THE   PREPARATION 

OF 

ORGANIC  COMPOUNDS 


BY 
E.  DE  BARRY  BARNETT 

B.Sc.(Lond.)  A.I.C. 


WITH  50  ILLUSTRATIONS 


PHILADELPHIA 
P.   BLAKISTON'S   SON  &  CO. 

1012    WALNUT    STREET 
1912 


Printed  in  Great  Britain 


PREFACE 

IN  the  present  volume  the  Author  has  aimed  at  giving 
a  general  outline  of  the  methods  actually  employed  in 
preparing  organic  compounds,  and  thus  providing  not 
only  a  laboratory  manual,  but  also  a  book  which  may 
be  used  as  a  companion  volume  to  the  usual  theoretical 
text -books. 

In  the  first  chapter  will  be  found  a  short  description 
of  the  most  common  apparatus  and  reagents  u'sed  in 
preparative  organic  work  ;  and  although  some  of  the 
apparatus  described  may  be  regarded  as  rather  crude 
for  academic  practice,  it  must  be  borne  in  mind  that 
the  average  works  laboratory,  at  all  events  in  this 
country,  is  not  fitted  with  all  the  latest  refinements, 
and  that  one  of  the  chief  difficulties  experienced  by  the 
young  chemist  on  first  entering  works  is  to  adapt 
himself  to  his  environment.  Although  to  some  minds 
the  idea  of  carrying  out  chemical  preparations  in  sauce- 
pans, jam-pots,  &c.,  may  seem  rather  bizarre,  experience 
will  show  that  such  apparatus  is  quite  as  satisfactory 
and  considerably  less  expensive  than  the  more  con- 
ventional and  more  brittle  beakers  and  basins. 

The  description  of  the  processes  given  is  less  full 
than  in  most  books  on  organic  preparations,  but  the 
details  given  are  sufficient  to  enable  the  average  student 
to  carry  out  the  preparations  successfully,  without 
being  so  exhaustive  as  to  reduce  his  work  to  mere 


281596 


vi  PREFACE 

mechanical  routine.  The  book  is  not  intended  for 
those  who  are  endeavouring  to  study  chemistry  by 
correspondence  lessons,  and  those  working  in  a  univer- 
sity or  technical  college  laboratory  can  usually  refer  to 
a  senior  student  or  to  a  member  of  the  staff  when  in 
difficulties. 

The  nomenclature  used  is,  in  most  cases,  the  same 
as  that  employed  in  Beilstein's  "  Handbuch."  In 
cyclic  compounds  the  substituent  with  the  lowest 
molecular  weight  is  placed  at  i.  In  calculating  the 
molecular  weight  of  groups,  — NHR  and  — NR2  are 
regarded  as  equivalent  to  — NH2,  — OR  is  regarded  as 
equivalent  to  —OH,  —  COOR  as  equivalent  to  — COOH, 
and  so  on,  where  R  is  an  organic  radical,  halogen 
atom,  &c.  Thus  C6H3[i]CH3[3]NO2[4]OH  is  3.  nitro- 
^-cresol,  C6H3[i]NMe2[2]OH[4]NO  is  2.  oxy-#-nitroso- 
dimethylaniline.  A  full  description  of  this  system  will 
be  found  in  the  introduction  to  vol.  i  of  Beilstein's 
"  Handbuch." 

A  considerable  number  of  the  preparations  have  been 
taken  from  the  patent  literature,  and  by  this  means  it 
is  hoped  to  familiarise  the  academic  chemist  with  a 
much  neglected  branch  of  the  literature.  German 
specifications  are  more  readily  accessible  than  English, 
and  will  be  found  in  Friedlander's  "  Fortschritte  der 
Teerfarben-fabrikation,"  vols.  i-ix,  1877-1910,  or  in 
Winther's  "  Patente  der  Organischen  Chemie,"  vols. 
i-iii,  1877-1905.  Abstracts  of  the  more  recent 
patents  will  be  found  in  the  "  Chemisettes -Zentralblatt," 
the  "  Journal  of  the  Chemical  Society,"  and  in  the 
various  technical  publications. 

The  Author  wishes  to  acknowledge  his  indebtedness 
to  the  classical  works  of  Lassar-Cohn  •("  Arbeit s- 
methoden ")  and  Theodor  Weyl  ("  Methoden  der 


PREFACE  vi 

organischen  Chemie  "),  and  to  express  the  hope  that 
this  small  volume  may  be  the  means  of  causing  their 
treatises  to  be  better  known  in  this  country.  Where 
other  authorities  have  been  consulted,  an  acknowledg- 
ment will  be  found  in  the  footnotes. 

The  Author  also  wishes  to  express  his  thanks  to 
Mr.  A.  M.  Hutchison,  B.Sc.,  Mr.  H.  J.  Page,  B.Sc., 
and  to  Mr.  W.  G.  Prescott,  B.Sc.,  A.I.C.,  for  much 
valuable  help  while  the  book  was  passing  through  the 
press.  His  thanks  are  also  due  to  Messrs.  Baird  and 
Tatlock  for  kindly  lending  some  of  the  blocks  used 
for  the  illustrations. 

E.  DE  BARRY  BARNETT 

9  COLLINGHAM  ROAD,  S.W. 


CONTENTS 


CHAPTER  I 

APPARATUS,  METHODS  OF  MANIPULATION, 
REAGENTS 

APPARATUS  PAGE 

Flasks  ! 

Basins  2 
Beakers 

Dropping  funnels 

Condensers  ^ 

Stirring  ? 

Baths  g 

Freezing  mixtures  3 

Filtration  3 

Vacuum  pumps  I  r 

Work  under  pressure  !  l 

MANIPULATION 

Solvents  and  crystallisation  I  e 

Drying  solids  2  j 

Extracting  liquids  2I 

Distillation  22 

Sublimation  2- 

Melting-points  23 

Boiling-points  2p 

REAGENTS 

Sulphuric  acid  3O 

Hydrochloric  acid  30 
Nitric  acid 

Ammonia  -j 

Caustic  soda  |j 
Aluminium  chloride 

Cuprous  chloride  ^ : 

Cuprous  bromide  ^2 

Sodium  ethoxide  ,  ~ 

Test-papers  || 
ix 


x  CONTENTS 

CHAPTER  II 
THE  HYDROCARBONS 

(i )  From  the  halogen  compounds  FAGE 

(a)  Retrogressive  substitution  35 

(b)  Action  of  metals  35 

(c)  Loss  of  halogen  acid  38 
(ii)  From  the  alcohols 

(a)  Loss  of  water  39 

(6)  Reduction  4i 

(iii)  From  the  aldehydes  and  ketones  41 

(iv)  From  the  unsaturated  compounds  42 

(v)  By  Friedel-Craft's  reaction  42 
(vi)  From  the  diazo-salts 

(a)  By  replacing  the  diazo-group  by  hydrogen  44 

(6)  By  the  linking  of  the  aryl  residues  45 

(vii)  From  the  carboxylic  acids  46 

(viii)  From  the  lower  hydrocarbons  by  oxidation  47 


CHAPTER  III 
THE  HALOGEN  COMPOUNDS 

(i)  By  the  replacement  of  hydrogen  by  halogen 

(a)  Molecular  halogen  49 

(b)  Nascent  halogen  54 

(c)  Halogen  compounds 

(1)  Phosphorus  halides  56 

(2)  Sulphur  halides  57 

(3)  Antimony  pentachloride  59 

(4)  Sulphuryl  chloride  59 

(5)  Iodine  chloride  60 

(6)  Bleaching  powder  61 
(ii)  By  the  addition  of  halogen  or  halogen  acid 

(a)  Addition  of  halogen  61 

(b)  Addition  of  halogen  acid  63 
(iii)  By  the  replacement  of  oxygen  or  hydroxyl  by  halogen 

(1)  Phosphorus  pentachloride  64 

(2)  Phosphorus  oxy chloride  66 

(3)  Phosphorus  trichloride  68 

(4)  Halogen  acid  69 

(5)  Thionyl  chloride  71 

(6)  Sulphuryl  chloride  73 

(7)  Chlorsulphonic  acid  73 

(8)  Benzene  sulphochloride  74 

(9)  Carbonyl  chloride  74 
(iv)  By  the  replacement  of  the  diazo-group  by  halogen 

(a)  Method  of  Griess  74 

(b)  Method  of  Sandmeyer  75 

(c)  Method  of  Gattermann  75 


CONTENTS  xi 

ADDENDA  PAGE 

Chloroform  78 

lodoaryldichlorides  78 

Replacement  of  chlorine  or  iodine  by  bromine  76 

Replacement  of  bromine  or  iodine  by  chlorine  79 

Replacement  of  chlorine  or  bromine  by  iodine  80 

Phosgene  80 

CHAPTER  IV 
THE  ALCOHOLS,  PHENOLS,  AND  MERCAPTANS 

A.  THE  ALCOHOLS  AND  PHENOLS 

(i)  By  the  hydrolysis  of  the  esters  82 

(ii )  From  the  halogen  compounds  82 

(iii)  From  the  sulphonic  acids  85 

(iv)  By  Grignard's  reaction  85 

(v)  From  the  amines  88 

(vi)  By  the  reduction  of  the  aldehydes  and  ketones  91 

(vii)  From  the  unsaturated  compounds  96 
(viii)  From  the  aldehydes  by  condensation 

(a)  Aldol  condensation  97 

(b)  Benzoin  condensation  97 

(c)  Lederer-Manasse  condensation  97 

(d)  Diaryl-carbinol  synthesis  100 
(ix)  From  the  hydrocarbons  by  oxidation  101 
(x)  From  the  quinones  by  the  addition  of  phenols  102 
(xi)  By  the  rearrangement  of  the  a-diketones  104 

B.  THE  MERCAPTANS  104 

CHAPTER  V 

THE  ALDEHYDES,  KETONES,  QUINONES  (AND  QUINONE- 
IMIDES),  AND  SOME  DERIVATIVES  OF  THE  SAME 

A.  THE  ALDEHYDES 

(i)  By  the  oxidation  of  primary  alcohols  109 
(ii)  By  the  oxidation  of  aromatic  hydrocarbons 

1 i )  Chromyl  chloride  112 

(2 )  Chromic  acid  112 

(3)  Cerium  dioxide  113 

(4)  Indirect  oxidation  114 
(iii)  By  the  reduction  of  the  acids  1 16 
(iv)  By  the  aldol  condensation  117 
(v)  By  condensation  with  ethyl  formate  1 1 9 
(vi)  By  the  replacement  of  hydrogen  by  — CHO  120 

B.  THE  KETONES 

(i)  From  the  acids  122 

(ii)  By  the  oxidation  of  the  alcohols  123 

(iii)  By  the  oxidation  of  the  methylene  group  126 


xii  CONTENTS 

PAGE 

KETONES— continued 

(iv)  By  Friedel-Craft's  reaction  127 

(v)  From  phthalic  anhydride  129 

(vi)  By  the  hydrolysis  of  the  t'so-nitroso  compounds  1 30 

(vii)  By  the  benzoin  condensation  13° 
(viii)  By  Claisen's  reaction  (acetoacetic-ester  synthesis)      131 

C.  THE  QUINONES 

By  the  oxidation  of 

(a)  Hydrocarbons  137 

(b)  Primary  amines  i38 

(c)  Ami  no -phenols  139 

(d)  Dihydric  phenols  i42 

D.  DERIVATIVES  OF  ALDEHYDES  AND  KETONES 

Oximes  H3 

Semicarbazones  1 44 

Thiosemicarbazones  145 

Aminoguanidine  derivatives  145 

Phenylhydrazones  146 

Osazones  146 


CHAPTER  VI 
THE  ETHERS  AND  SULPHIDES 

A.  THE  ETHERS  148 

B.  THE  SULPHIDES  150 

CHAPTER  VII 

THE  CARBOXYLIC  ACIDS,  THEIR  ANHYDRIDES  AND 
ESTERS 

A.  THE  CARBOXYLIC  ACIDS 

(i)  By  the  hydrolysis  of  the  nitriles,  chlorides,  and  amides  153 
(ii)  By  the  oxidation  of    the  alcohols,  aldehydes,  and 

ketones  1 5  5 

(iii)  By  the  oxidation  of  alkyl  groups  1 57 

(iv)  By  Grignard's  reaction  161 

(v)  By  Kolbe's  method  161 
(vi)  From  the  aldehydes  and  ketones  by  condensation 

(a)  Perkin's  reaction  164 

(b)  Claisen's  reaction  167 
(vii)  From  acetoacetic  ester  and  malonic  ester  169 

ADDENDA 

The  benzylic  acids  i72 

The  o.-benzoyl  benzoic  acids  173 

The  syw-diphenylmethane  dicarboxylic  acids  173 


CONTENTS  xiii 

B.  THE  ACID  ANHYDRIDES  PAGE 

(i)  By  heating  the  acid  with  acetic  anhydride  174 

(ii)  By  heating  the  acid  chloride  with  the  sodium  salt  175 
(iii)  By  treating  the  acid  chloride  with  quinoline  or  pyri- 

dine  175 

C.  THE  CARBOXYLIC  ESTERS 

(i)  Esterification  of  the  acid  by  the  alcohol  177 

(ii)  By  the  action  of  the  acid  chloride  on  the  alcohol  178 

(iii)  By  the  action  of  the  acid  anhydride  on  the  alcohol  180 

(iv)  Esterification  with  dimethyl  sulphate  1 80 

(v)  By  the  action  of  the  silver  salt  on  the  alkyl  iodide  181 

D.  ESTERS  OF  INORGANIC  ACIDS  182 


CHAPTER  VIII 
THE  NITRILES  OR  CYANIDES 

(i)  From  the  acid  amides  185 

(ii)  From  the  halogen  compounds  186 

(iii)  From  the  diazo-compounds  187 
(iv)  By  the  addition  of  hydrocyanic  acid  to  aldehydes 

and  ke tones  188 

(v)  By  the  addition  of  hydrocyanic  acid  to  quinones  191 

CHAPTER  IX 

THE  NITROSO-  (AND  iso-NITROSO-)  AND  NITRO- 
COMPOUNDS 

A.  THE  NITROSO-COMPOUNDS 

(i)  By  the  oxidation  of  the  amines  193 

(ii)  By  the  oxidation  of  the  hydroxylamines  194 

(iii)  By  the  addition  of  N2O3  or  NOC1  195 

(iv)  The  nitroso-phenols  and  aromatic  nitroso-tertiary 

amines  195 

(v)  The  nitrosamines  197 

(vi)  The  fc'so-nitroso-compounds  198 

B.  THE  NITRO-COMPOUNDS 

ALIPHATIC  NITRO-COMPOUNDS 

(i)  By  direct  nitration  199 

(ii)  By  the  replacement  of  halogen  199 

AROMATIC  NITRO-COMPOUNDS 
Nitration  with 

(1)  Nitric  acid  alone  201 

(2)  Nitric  acid  and  an  organic  solvent  201 

(3)  Mixed  acids  202 


xiv  CONTENTS 

ADDENDA  PAGE 

The  picrates  206 

The  nitrodiphenyl  methanes  207 


CHAPTER  X        - 
THE  AMINO-COMPOUNDS 

A.  PRIMARY  COMPOUNDS 

(i)  By  the  reduction  of  the  nitro -compounds 

(1)  Metal  and  acid  208 

(2)  Alkali  sulphides  211 

(3)  Hydro  sulphite  213 
(ii)  By  the  reduction  of  the  azo -compounds  214 
(iii)  By  the  benzidine  and  semi  dine  change  217 
(iv)  By  the  replacement  of  halogen  atoms  218 
(v)  By  the  replacement  of  hydroxyl  groups  220 
(vi)  By  the  disruption  of    the  acid  amides  (Hofmann's 

reaction)  223 

(vii)  From  the  nitriles  224 

B.  THE  SECONDARY  AND  TERTIARY  COMPOUNDS 

(i)  From  the  halogen  compounds  225 
(ii)  By  heating  the  primary  base  with  its  hydrochloride      231 

(iii)  By  heating  the  amines  with  iodine  231 

(iv)  By  the  rearrangement  of  the  oximes  (Beckmann 

change)  232 

ADDENDA 

The  benzylidene  derivatives  233 

Urea  233 

Thioamides  and  thioanilides  234 


CHAPTER  XI 

THE  DIAZO-,  DIAZOAMINO-,  DIAZOIMINO-,  AZO-,  AZOXY- 
AND  HYDRAZO-COMPOUNDS 

A.  THE  DIAZO-COMPOUNDS  237 

B.  THE  DIAZOAMINO-COMPOUNDS  242 

C.  THE  DIAZOIMIDES  245 

D.  THE  AZO-COMPOUNDS  247 

E.  THE  AZOXY-COMPOUNDS  254 

F.  THE  HYDRAZO-COMPOUNDS  255 

G.  THE  HYDRAZINES  256 


CONTENTS  xv 

CHAPTER  XII 
THE  SULPHINIC  AND  SULPHONIC  ACIDS 

PAGE 

A.  THE  SULPHINIC  ACIDS  258 

B.  THE  SULPHONIC  ACIDS 

(i)  By  direct  sulphonation  260 

(ii)  By  the  oxidation  of  the  sulphinic  acids  266 

CHAPTER  XIII 
MISCELLANEOUS  TYPES 

A.  THE  PYRAZOLONES  268 

B.  THE  ACRIDONES  269 

C.  THE  XANTHONES  270 

D.  THE  THIOXANTHONES  270 

E.  THE  PHENOXAZINES  271 

F.  THE  THIAZINES  274 

G.  THE  AZINES  276 
H.  THE  QUINOLINES  AND  ISOQUINOLINES 

(i)  Skraup's  synthesis'  279 

(ii)  Baeyer's  synthesis  283 

(iii)  Niementowski's  synthesis  287 

I.  THE  TRIPHENYLMETHANE  GROUP  288 

(i)  The  malachite-green  dyes  288 

(ii)  The  rosaniline  dyes 

(a)  Condensation  of  £-aminobenzaldehydes  with 

ami  no -compounds  291 

(6)  Phosgene  process  293 

(c)  New-fuchsin  process  294 

(iii)  The  rosolic  acid  dyes  296 

(iv)  The  phthaleins  and  pyronines  297 

J.  INDIGO  298 

K.  THE  INDAMINES  AND  INDOPHENOLS  300 


ABBREVIATIONS 


A  Annalen  der  Chemie. 

A.  Ch.  Annales  de  Chimie  et  de  Physique. 
Am.  American  Chemical  Journal. 

Am.  Soc.  Journal  of  the  American  Chemical  Society. 

B.  Berichte  der  Deutschen  Chemischen  Gesellschaft. 
Bl.  Bulletin  de  la  Societe  Chimique  de  Paris. 

C.  Chemisches  Zentralblatt. 

C.  r.  Comptes  rendues  de  1' Academic  des  Sciences. 

Ch.  Z.  Chemiker-Zeitung  (Cothen). 

D.R.P.  Patentschrift  des  Deutschen  Reiches. 

E.P.  English  Patent  Specification. 

F.P.  French  Patent  Specification. 

G.  Gazetta  chimica  itialiana. 

H.  Hoppe-Seyler's  Zeitschrift  fur  physiologische  Chemie. 

JJahresbericht  der  Chemie. 

.  pr.  Journal  fiir  praktische  Chemie. 

.R.C.S.  Journal  of  the  Russian  Chemical  Society. 

M.  Monatshefte  der  Chemie. 

Pat.  Anm.  Patent  Anmeldung. 

Proc.  Proceedings  of  the  Chemical  Society. 

R.  Recueil  des  travaux  chimique  des  Pays-Bas. 

Soc.  Journal  of  the  Chemical  Society. 

Z.  Zeitschrift  fur  Chemie. 

Z.  a.  Ch.  Zeitschrift  fiir  angewandte  Chemie. 

Z.  El.  Ch.  Zeitschrift  fiir  Elektrochemie. 

With  one  or  two  exceptions,  the  above  abbreviations  are  those 
used  in  Beilstein's  "  Handbuch  "  and  Richter's  "  Lexikon." 


xvi 


CHAPTER  I 


APPARATUS,  METHODS  OF  MANIPULATION, 
REAGENTS 

APPARATUS 

FLASKS.  The  ordinary  flat-bottomed  flasks,  round 
flasks,  and  conical  (Erlenmeyer)  flasks  are  all  suitable 
for  organic  preparations.  The  last -mentioned  have  the 
great  advantage  that  they  are  readily  cleaned.  Cork 
rings  or  wicker  baskets  (Fig.  i)  should  be  provided  for 
standing  round-bottom  flasks 
on  the  bench.  Flasks  can 
sometimes  be  replaced  by 
enamelled-ware  cans,  but  these 
suffer  from  the  great  dis- 
advantage of  not  allowing  the 
liquid  to  be  seen.  They  are 
useful,  however,  when  a  liquid 
bumps  heavily.  For  experi- 
ments at  the  ordinary  tem- 
perature bottles  are  preferable 
to  flasks,  as  there  is  less  like- 
lihood of  breakage.  Bottles 
of  good  glass  will  stand  heating  to  100°  on  the 
water-bath,  provided  the  temperature  is  raised  slowly. 
Experiments  with  concentrated  sulphuric  acid  or 
oleum  are  best  carried  out  in  cast-iron  or  lead  vessels 
(Fig.  2),  provided,  of  course,  no  oxidising  agent  is 
present.  Lead  vessels  can  easily  be  made  from  lead 
pipe  by  any  lead-burner.  No  solder  must  be  used, 
all  joints  being  "  burned."  A  convenient  size  is  15  cm. 
deep  by  6  cm.  diameter.  They  must  always  be  heated 


FIG.  i. 


2  %  PREPARATION  OF  ORGANIC  COMPOUNDS 

by  means  of  an  oil-bath.  The  lid  is  held  in  position  by 
nieans  of  four  thumb-screws. 

Distilling  Flasks  are  discussed  on  p.  23. 

BASINS.  Porcelain  basins  can  be  replaced  in  prac- 
tically all  cases  by  enamelled  basins,  saucepans,  &c. 
These  should  be  of  the  best  quality,  and  once  the  enamel 


FIG.  2. 


FIG.  3. 


FIG.  4. 


has  begun  to  chip  care  must  be  taken  not  to  use  them 
for  acid  liquids. 

BEAKERS.  Ordinary  thin  glass  beakers  are  not 
much  used  as  they  can  generally  be  replaced  by  sauce- 
pans. For  experiments  which  do  not  require  heating 
thick  glass  beakers  are  very  convenient.  These  are 
especially  useful  when  the  liquid  has  to  be  stirred  ; 
for  example,  in  preparing  diazo-solutions.  Jam-pots 
make  excellent  thick  glass  beakers. 


APPARATUS,  METHODS,  REAGENTS       3 

DROPPING  FUNNELS.  Dropping  funnels  are  illus- 
trated on  p.  22.  A  very  convenient  form  is  the  Walter 
funnel  (Fig.  3),  as  this  allows  the  rate  at  which  the 
liquid  is  being  added  to  be  seen  with  great  ease. 

CONDENSERS.  The  Liebig  condenser  (Fig.  4)  is 
the  most  usual  form,  but  spiral  condensers  (Fig.  5) 
are  very  efficient.  An  inexpensive  spiral  condenser 
is  readily  made  by  coiling  lead  gas- 
pipe  and  arranging  it  with  the  lower 
end  passing  through  the  top  of  an 
inverted  bell-jar  (Fig.  6).  The  cooling 
water  is  led  in  by  the  pipe  A  and  is 


FIG.  5. 


FIG.  6. 


FIG.  7. 


removed  by  the  siphon-tube  B.   These  condensers  should 
not  be  used  when  the  distillate  is  apt  to  solidify. 

Reflux  Condensers  are  condensers  arranged  so  that 
the  condensed  liquid  flows  back  into  the  flask.  They 
are  either  arranged  in  a  vertical  position  (Fig.  7)  or 
sloped  (Fig.  8).  The  latter  arrangement  is  the  more 
convenient  when  a  retort  is  being  used.  The  bulb 
condenser  shown  in  the  diagram  is  more  efficient  than 
the  ordinary  Liebig  condenser,  but  is  not  suitable  for 
distillations.  Double -surf  ace  condensers  are  very 


4    PREPARATION  OF  ORGANIC  COMPOUNDS 

suitable  for  refluxes,  especially  when  a  Soxhlet  extrac- 
tion apparatus  is  being  used.  Several  forms  are  on 
the  market,  of  which  two  are  shown  in  the  illustrations 
(Figs.  9  and  10). 


FIG.  8. 

When  an  agitator  is  used  in  conjunction  with  a  reflux 
condenser,  a  mercury  seal  (Fig.  n)  must  be  used.  The 
tube  A  passes  through  the  cork  of  the  flask  and  is 
attached  to  the  wide  tube  B  by 
means  of  a  cork.  The  tube  c 
is  attached  to  the  agitator  and 
reaches  very  nearly  to  the 
bottom  of  the  tube  B,  which 
is  then  filled  with  mercury. 

When  it  is  desired  to  keep 
the  water  in  the  condenser  at 
a  definite  temperature,  the 
arrangement  shown  in  Fig.  12 
is  simple  and  effective.  The 
water  from  the  tap  enters  the 
bucket  A  at  B.  It  leaves  by  the 
siphon-tube  E,  the  rate  of  flow 
being  regulated  by  the  screw 
clip  D.  The  temperature  at  JTIG.  9. 

which  it  enters  the   condenser 

is  taken  at  c  as  shown.  The  large  bulk  of  water 
in  the  bucket  prevents  any  rapid  variation  in  the 
temperature.  By  keeping  ice  in  A  this  arrangement 
can  be  used  when  very  easily  volatile  liquids  are  being 


APPARATUS,  METHODS,  REAGENTS       5 

distilled  and  it  is  desired  to  have  the  condenser  water 

as  cold  as  possible. 

STIRRING.     Most  reactions  proceed  best  when  the 

reacting  mixture  is  well 
stirred.  The  most  effec- 
tive source  of  power  in 
the  laboratory  for  driving 
agitators  is  Rabe's  turbine 
(Fig.  13).  It  is  convenient 
to  connect  this  with  the 
water-supply  by  means  of 
thick-walled  rubber  tubing 
or  flexible  metal  tubing,  as 
it  can  then  be  readily 
adjusted  to  any  desired 
position.  For  most  pur- 


Jluifier 
band—* 


FIG.  10. — Burgess  condenser. 


FIG.  ii. 


poses  the  agitator  is  simply  made  by  bending  a  piece  of 
thick  glass  rod  as  shown  (Fig.  14).  It  is  fixed  in  the 
pulley  A  by  means  of  corks,  and  is  held  in  position  by 
clamping  the  loose  brass  tube  B.  When,  however,  the 


6    PREPARATION  OF  ORGANIC  COMPOUNDS 

liquid  contains  a  heavy  precipitate,  such  as  zinc  dust, 
the  agitator  shown  in  Fig.  15  is  more  effective. 

The  agitator  is  driven  from  the  turbine  by  means  of 
an  endless,  round  rubber  band.  In  order  to  join  the 
ends  of  this  so  that  it  will  not  "  jump  "  the  wheel, 


FIG.  12. 

they  are  cut  off  at  as  accurate  an  angle  as  possible, 
and  the  tapering  ends  then  bound  firmly  together  with 
stout  thread.  Liquids  can  also  be  agitated  by  blowing 
air  through  them,  or  by  sucking  it  through  by  means  of 
a  water-pump  (Fig.  16). 

BATHS.     Cast-iron  saucepans  make  the  best  baths. 
For  temperatures  up  to  100°  of  course  water  is  used. 


APPARATUS,  METHODS,  REAGENTS       7 

For  temperatures  above  100°  an  oil-  or  fusible -metal 

bath  must  be  employed.     As  an  oil,  castor  oil,  cylinder 

oil,  or  paraffin  wax  is  suitable,  and  can  be  used  for 

temperatures    up    to    about 

300°.      As    fusible  metals, 

Wood's  alloy,  melting  at  71° 

(i  to  2  parts  Cd,  2  parts  Sn, 

7  to  8  parts  Sb),  and  Rose's 

metal,  melting  at  95°  (2  parts 

Sb,  I  part  Pb,  i  part  Sn),  are 

the    most    suitable.      When 

using     a    metal-bath     it    is 

advisable  to   coat   the    flask 

with  lamp-black  in  order  to 

prevent   the   metal  adhering 

to    the    glass.       Metal-baths 


FIG.  13. 


have  the  advantage  of  being  cleaner  than  oil-baths, 
and,  owing  to  the  high  conductivity  of    the  metaL 


FIG.  14. 


FIG.  15. 


are  less  liable  to  local  overheating,  but  they  have 
the  disadvantage  that  considerable  force  is  required 
to  immerse  the  flask  in  the  relatively  dense  metal, 
and  hence  there  is  increased  liability  of  breakage. 


PREPARATION  OF  ORGANIC  COMPOUNDS 

If  steam  is  available,  a  steam-bath  can  be  con- 
veniently substituted  for  a 
water  -  bath.  A  simple  and 
easily  constructed  form  is 
shown  in  Fig.  17.  The  steam 
is  led  in  at  A  and  the  con- 
densed water  passes  out  at  B. 
These  steam-baths  are  espe- 
cially useful  when  very  easily 
inflammable  liquids,  such  as  car- 
bon bisulphide,  which  ignites 
when  brought  in  contact  with 
metallic  surfaces  at  160°,  are 
being  heated,  as  the  steam  can 
be  generated  at  a  distance. 

FREEZING  MIXTURES. 
Powdered  ice  and  common  salt 


FIG.  1 6. 


(3  parts  ice,  i  part  NaCl)  gives 
a  temperature  of  about  — 18° ; 
ice  and  crystallised  calcium 
chloride  (7  parts  ice,  10  parts 
CaCl26H2O)  about  -  48°.  Ice 
and  hydrochloric  acid  also  form 
an  efficient  freezing  mixture.  If 
lower  temperatures  are  desired, 
solid  carbon  dioxide  ( —  78°)  or 
liquid  air  ( - 180°)  must  be 
used.  The  former  is  most  effec- 
tive when  mixed  to  a  slush  with 
alcohol  or  ether. 

FILTRATION.  Organic  pre- 
parations are  not  often  filtered 
through  an  ordinary  conical 
funnel.  These  are  useful,  how- 
ever, when  solutions  which  crys- 
taDise  readily  on  cooling  are 
being  dealt  with,  as  they  can 
be  readily  "  jacketed."  A  simple 


FIG.  17. 


and  quite  effective  jacket  is  made  by  wrapping  the 
funnel  round  with  a  spiral  of  rather  narrow  lead  pipe, 


FIG.  1 8. 


APPARATUS,  METHODS,  REAGENTS       9 

the  turns  of  the  spiral  being  made  as  close  as  possible, 
and  then  blowing  steam  through  during  the  nitration. 

A  more  convenient  form  is 
shown  in  Fig.  18.  It  con- 
sists of  a  double  -  walled 
copper  cone  which  carries 
the  glass  funnel.  The  annu- 
lar space  is  filled  with  water 
which  is  heated  as  shown. 
Before  filtering  inflammable 
liquids  such  as  alcohol,  ben- 
zene, &c.,  the  burner  must 
be  removed.  The  most  effec- 
tive form  of  filter  jacket  is 
that  shown  in  Fig.  19.  It 
consists  of  a  double-walled 

glass  funnel,   arrangements  being  made  for  passing 
steam  through  the  annular  space.     The  advantage  of 
this  type  lies  in  the  fact  that  the  paper  is  in  actual 
contact  with  the  heated 
surface. 

Usually  liquids  are 
filtered  through  a 
Buchner  (Fig.  20)  or 
Hirsch  (Fig.  21)  funnel. 
The  paper  is  placed  on 
the  perforated  porce- 
lain disc  A,  moistened 
with  the  liquid  to  be  fil- 
tered, and  well  pressed 
down.  The  funnel  is 
connected  with  a  thick- 
walled  flask  by  means 
of  a  rubber  cork,  and 
the  side-tube  of  the  FlG 

flask  connected  to  the 

pump.  Thin  glass  flasks  must  not  be  used  as  they 
collapse.  The  Hirsch  model  is  chiefly  used  when  small 
quantities  are  being  dealt  with. 

As  filtering  media  Schleicher  and  Schull's  hardened 


FIG.  20. 


10        PREPARATION  OF  ORGANIC  COMPOUNDS 

paper  No.  575  white  band  is  the  most  generally  useful 
and  will  stand  fairly  strong  cold 
acids.  It  is  somewhat  expen- 
sive, but  after  use  can  be  cleaned 
with  a  nail-brush  and  used  again. 
It  is  not  suitable  for  filtering 
organic  solvents  such  as  ben- 
zene, nitrobenzene,  aniline,  &c., 
through  a  Buchner  funnel,  as 
when  moistened  with  oily  liquids 
it  will  not  adhere  to  the  surface 
of  the  plate.  For  such  liquids 
Schleicher  and  Schiiirs  595 
white  band  will  be  found  satis- 
factory. Cloth  also  makes  an 
excellent  medium,  unbleached 
calico  being  the  most  satisfac- 
tory. It  is  either  cut  into  circles 
and  used  with  a  Buchner  funnel 
in  the  ordinary  way,  or  it  is 
suspended  from  a  wooden  frame  as  shown  (Fig.  22). 
The  precipitate  can  be  effec- 
tively freed  from  mother-liquor 
by  folding  up  the  cloth  just  as 
a  parcel  is  wrapped  up,  and 
then  pressing  either  in  an  ordi- 
nary ledger  press,  or,  if  this  is 
not  available,  by  piling  bricks 
on  it.  When  pressing  precipi- 
tates it  is  advisable  to  use 
a  double  thickness  of  cloth. 
Highly  corrosive  liquids  such 
as  concentrated  sulphuric  acid, 
caustic  alkali,  &c.,  must  be 
filtered  through  glass-wool  or 
asbestos.  Glass-wool  is  used 
in  the  form  of  a  small  plug  in 
an  ordinary  conical  funnel,  but 
care  must  be  taken  not  to  pack  it  too  tight.  An 
asbestos  filter  is  prepared  on  a  Buchner  funnel  just 


FIG.  21. 


APPARA1US,  METHODS,  REAGENTS      n 

as  in  a  Gooch  crucible.     It  is  much  more  satisfactory 
than  glass-wool. 

VACUUM  PUMPS.  There  are  numerous  forms  of 
water-pumps  on  the  market,  of  which  that  shown  in 
the  diagram  (Fig.  23)  is  one  of  the  most  effective. 
It  is  connected  with  the  water-supply  by  thick-walled 
rubber  tubing  and  must  be  carefully  wired  on.  With 
a  good  water-pressure,  a  vacuum  of  about  10  mm. 
of  mercury  can  be  obtained.  To  obviate  the  danger  of 


FIG.  22. 

the  water  running  back,  an  extra  thick-walled  flask 
is  interposed  between  the  pump  and  the  vessel  which  is 
being  exhausted. 

For  measuring  the  pressure  a  mercury  manometer 
as  shown  in  Fig.  24  is  most  suitable.  When  the  experi- 
ment is  finished  great  care  must  be  taken  to  admit  air 
very  slowly,  as  if  the  air  be  admitted  rapidly  the  mer- 
cury will  rush  up  and  break  the  top  of  the  tube. 

WORK  UNDER  PRESSURE.  *When  experiments 
are  to  be  carried  out  under  only  slightly  elevated 
pressure  (not  more  than  one  atmosphere),  soda- 
water  bottles  or  beer  bottles  can  be  used.  These 


12        PREPARATION  OF  ORGANIC  COMPOUNDS 

must  be  wrapped  up  in  stout  cloth  and  heated  very 
slowly  on  a  water-bath.     It  is  not  safe  to  heat  them 


FIG.  24. 


FIG.  23. 


FIG.  25. 


above  100°.  For  higher  pressures  a  bomb  tube  or  an 
autoclave  must  be  used.  Bomb  tubes  are  made 
of  good  quality  glass  tubing  about  16  mm.  internal 
diameter  and  about  3  mm.  thickness  of  wall.  It  is 


APPARATUS,  METHODS,   REAGENTS  13 

not  necessary  to  use  hard  glass,  Jena  "  resistance  " 
glass  (blue  line  and  stamped  "  R  ")  or  Jena  "  normal 
glass  "  (red  line)  being  the  most  suitable,  as  they  are 
easily  worked  in  an  ordinary  gas-air  blowpipe.  One 
end  of  the  tube  is  carefully  sealed  off  in  the  ordinary 
way,  care  being  taken  to  avoid  leaving  a  "  blob  "  of 
glass.  The  tube  is  then  filled  (it  must  not  be  more 
than  half  full),  the  open  end  carefully  cleaned  and  dried, 


FIG.  26. 


and  then  drawn  off  to  a  thick  capillary.  To  do  this  it 
is  gradually  heated  in  the  blowpipe  until  soft  and  a 
piece  of  glass  rod  about  6  in.  long  attached  as  shown 
(Fig.  25) .  The  blast  flame  is  then  lowered  until  it  is  about 
4  in.  long,  made  as  hot  as  possible,  and  allowed  to  play 
on  the  bomb  tube  about  •£•  in.  below  the  end.  The 
tube  is  held  in  as  horizontal  a  position  as  its  contents 
will  allow  and  continually  revolved,  the  open  end  being 
supported  by  holding  the  glass  rod  with  the  left  hand. 
Under  this  treatment  the  glass  soon  thickens  and  begins 
to  fall  together  (Fig.  26).  When  almost  closed  the 
tube  is  removed  from  the  flame,  allowed  to  cool  for 


14        PREPARATION  OF.  ORGANIC  COMPOUNDS 

a  moment,  and  then  slowly  and  steadily  drawn  out  to  a 
capillary.  This  is  then  sealed  off  and  the  whole  carefully 
annealed  in  the  smoky  flame.  The  finished  tube  should 
present  the  appearance  as  shown  in  Fig.  27.  The  seals 
are  quite  simple  to  make,  but  require  a  little  practice. 
Points  to  remember  are  :  (i)  Do  not  draw  out  the 
capillary  until  the  sides  have  thickened  and  fallen 
in  so  that  the  tube  is  almost  closed ;  (2)  allow  the 
tube  to  cool  for  a  moment  before  drawing  out,  and 
draw  out  slowly  ;  (3)  reject  any  seal  in  which  the 
walls  of  the  capillary  and  the  shoulder  are  not  thick  ; 


FIG.  27. 

(4)  anneal  the  tube  thoroughly  in  the  smoky  flame. 
Well-sealed  tubes  will  stand  a  very  high  pressure. 

Bomb  tubes  are  wrapped  in  paper  (to  prevent 
their  being  scratched),  placed  in  a  cast-iron  pipe,  and 
then  heated  in  a  special  furnace  such  as  shown  (Fig.  28) . 
After  cooling  and  without  removing  the  tube,  the  end  of 
the  capillary  is  heated  with  a  flame  until  the  glass 
softens  and  any  pressure  is  blown  off.  When  there  is 
no  longer  any  pressure  in  the  tube  the  end  is  cut  off 
in  the  usual  way,  but  tubes  must  never  be  removed 
from  the  furnace  until  it  is  quite  certain  that  they 
contain  no  pressure.  As  the  capacity  of  bomb  tubes  is 
limited,  it  is  often  more  convenient  to  use  an  autoclave. 
These  are  constructed  of  steel  or  bronze,  and  if  desired 
can  be  lined  with  enamel,  lead,  &c.  The  lid  should  be 
provided  with  a  tube  to  carry  the  thermometer,  a 


APPARATUS,  METHODS,  REAGENTS  •  15 

pressure  gauge,  and  a  screw  valve.  An  agitator  can 
also  be  added,  but  under  high  pressure  the  stuffing- 
box  almost  invariably  leaks.  The  autoclave  itself  is 
provided  with  a  lead  ring  and  the  lid  is  screwed  into 
this  by  means  of  bolts.  The  autoclave  is  heated 
either  by  a  direct  flame  or  by  an  oil-bath. 


FIG.  28. 

SOLVENTS  AND  CRYSTALLISATION.    The 

majority  of  reactions  proceed  best  when  the  reacting 
substances  are  in  solution,  and  solvents  are  also  added 
to  moderate  an  otherwise  too  violent  reaction*  The 
purification  of  crude  solids  is  usually  carried  out  by 
recrystallisation.  In  choosing  a  solvent  one  should 
be  chosen  in  which  the  desired  substance  dissolves 
readily  on  heating,  but  in  which  it  is  almost  insoluble 
in  the  cold,  and  in  which  the  impurities  are  either 


1 6   PREPARATION  OF  ORGANIC  COMPOUNDS 

insoluble  or  are  very  soluble.  The  usual  procedure 
is  to  dissolve  the  substance  in  the  boiling  solvent, 
filter  the  hot  solution  from  any  insoluble  impurities, 
and  then  cool  the  nitrate  as  rapidly  as  possible  with 
violent  shaking.  Crystallisation  can  often  be  induced 
by  scratching  the  sides  of  the  vessel  with  a  glass  rod. 
As  substances  sometimes  separate  slowly  from  their 
solutions,  it  is  often  advisable  to  allow  the  whole  to 
stand  over-night  before  collecting  the  crystals.  These 
should  be  washed  with  the  solvent  from  which  they 
were  crystallised.  If  the  substance  separates  in  an 
oily  state  it  can  often  be  obtained  crystalline  by  re- 
crystallising  from  more  dilute  solutions.  If  it  does  not 
separate  at  all  the  solution  must  be  concentrated. 
Mixed  solvents,  especially  alcohol  and  water,  are  often 
very  useful.  They  are*  employed  as  follows.  The 
substance  is  dissolved  in  some  boiling  solvent,  e.g. 
alcohol,  in  which  it  is  readily  soluble.  A  second 
solvent,  e.g.  water,  which  is  miscible  with  the  first 
solvent,  but  in  which  the  substance  is  insoluble,  is  then 
slowly  added  until  a  slight  permanent  turbidity 
appears,  the  whole  being  kept  gently  boiling.  On 
cooling,  the  substance  will  usually  separate  in  the 
crystalline  form.  A  modification  of  this  method 
which  often  gives  excellent  results  is  carried  out  as 
follows.  The  substance  is  dissolved  in  some  cold 
solvent,  e.g.  water;  another  miscible  solvent,  e.g. 
alcohol,  in  which  the  substance  is  insoluble,  is  then 
added  until  a  slight  permanent  turbidity  appears. 
The  solution  is  then  filtered  and  placed  in  a  vacuum 
desiccator  over  some  substance  which  takes  up  the 
first  solvent  but  not  the  second ;  in  the  above  case, 
for  example,  soda -lime  or  solid  potash  would  be  used. 
The  solution  thus  becomes  less  and  less  rich  in  the 
solvent  which  has  the  power  of  dissolving  the  sub- 
stance, and  the  latter  separates  out,  usually  in  the 
crystalline  form.  As  a  last  resort  substances  which  are 
insoluble  in  water,  but  soluble  without  change  in 
concentrated  sulphuric  acid,  can  be  crystallised  by 
dissolving  in  the  concentrated  acid  and  then  setting 


APPARATUS,  METHODS,  REAGENTS  17 

the  solution  aside  in  a  moist  place,  e.g.  in  a  desiccator 
containing  water.  The  acid  gradually  becomes  more 
dilute,  and  the  substance  usually  separates  out 
crystalline. 

The  following  list  gives  the  solvents  most  generally 
used,  together  with  their  boiling-points  : 


Inorganic 
Solvents 

Water,  100° 
Cone.  H2SO4 
Cone.  HNO3 
Cone.  HC1 


Alcohols 

Methyl  alcohol,  66° 
Ethyl  alcohol,  78° 
Amyl  alcohol,  1 30° 


Hydrocarbons 

Petroleum  ether, 

70' 

Ligroin,  120° 
Benzene,  79° 
Toluene,  1 10° 
w.-Xylene,  139°, 
Naphthalene, 

M.P.  80°,  B.P.  218° 


Ethers 

Ether,  35°    * 
Anisole,  152° 


Bases 

Aniline,  182° 
Pyridine,  115° 
Quinoline,  239' 


Acids 

Formic  acid  (90  %) 
'  100° 
Acetic  acid,  119° 

Miscellaneous 
Compounds 

Acetone,  56° 
Carbon 

bisulphide,  47° 
Nitrobenzene,  210° 
Ethyl  acetate,  77° 
Ethyl  benzoate,  213' 


Phenols 

Phenol,  M.P.  43°, 
B.P.  181° 
w.-Cresol,  202° 

Halogen 
Compounds 

Chloroform,  61° 
Carbon  tetra- 

chloride,  78° 
Dichlorethylene, 

55° 
Trichlorethylene, 

88° 
Tetrachlor- 

ethylene,  121° 
Tetrachlor- 

ethane,  147° 
Pentachlor- 

ethane,  159° 
Epichlorhydrin, 

117° 

Chlorobenzene,  132° 
Bromobenzene, 

iS5c 
a-Chlor- 

naphthalene,  263° 
a-Brom- 

naphthalene,  279° 


Cone.  H2S04  is  only  used  as  described  on  p.  16. 
Cone.     HNO3    is    sometimes    useful     with    highly 
nitrated  compounds. 


1 8   PREPARATION  OF  ORGANIC  COMPOUNDS 

Alcohol.  In  most  laboratories  absolute  alcohol, 
containing  96-98  per  cent.  C2H5OH,  can  be  obtained 
duty-free.  In  a  large  number  of  cases,  especially 
when  used  as  a  solvent,  it  can  be  replaced  by  the  less 
expensive  methylated  spirit.  There  are  two  kinds  of 
methylated  spirit  on  the  market,  viz.  "  ordinary 
methylated  spirit/'  which  contains  10  per  cent,  of  wood- 
naphtha  and  not  less  than  0.385  per  cent,  of  mineral- 
naphtha  ;  and  "  industrial  spirit,"  which  contains  5-10 
per  cent,  of  wood-naphtha  but  no  mineral-naphtha. 
The  latter  of  these  is  the  more  suitable  for  laboratory 
purposes,  but  can  only  be  obtained  under  a  special 
licence.  Before  use  methylated  spirit  should  be 
purified  by  boiling  it  for  an  hour  under  a  reflux  con- 
denser with  a  little  solid  caustic  potash.  The  purified 
spirit  is  then  distilled  from  the  alkali  and  resin. 

Phenol  has  great  solvent  power,  but  suffers  from  the 
disadvantage  that  it  is  solid  at  the  ordinary  temperature. 
It  can  be  used  diluted  or  can  be  replaced  by  w.-cresol, 
but  is  not  much  used. 

Naphthalene  is  an  excellent  solvent,  but  on  account 
of  its  high  melting-point  it  finds  but  little  use  in 
recrystallising. 

Ether,  in  spite  of  its  high  solvent  power,  is  not  exten- 
sively used  for  recrystallisation,  as  substances  often 
do  not  separate  nicely.  This  can  be  remedied  to  a 
certain  extent  by  dehydrating  the  ether  over  sodium, 
but  its  low  boiling-point  is  a  great  objection. 

Pyridine  and  Quinoline  are  both  excellent  solvents 
and  are  usually  used  in  the  crude  form  as  obtained 
from  coal  tar. 

Ethyl  benzoate  is  an  excellent  solvent,  but  must  be 
used  with  care,  as  it  is  apt  to  benzoylate  phenols  and 
bases.  A  similar  objection  applies  to  all  esters  with 
high  boiling-points. 

A  high  boiling-point  solvent  is  best  removed  from 
the  crystals  by  washing  with  some  low  boiling-point 
liquid  with  which  it  is  miscible,  e.g.  ether.  If  the 
crystals  are  insoluble  in  water,  it  is  often  convenient 
to  remove  the  solvent  by  distillation  in  steam. 


APPARATUS,  METHODS,  REAGENTS      19 

DRYING  SOLIDS.  Solids  which  do  not  melt  or 
decompose  at  100°  are  best  dried  in  the  steam  oven 
unless  they  are  very  readily  vola- 
tile, e.g.  quinone.  The  Victor  Meyer 
oven  (Fig.  29)  forms  a  convenient 
method  of  drying  solids  at  any 
given  temperature.  It  consists  of 
a  double-walled  copper  box,  pro- 
vided with  a  lid,  the  annular  space 
being  provided  with  a  reflux  con- 
denser and  containing  a  liquid 
which  boils  at  the  temperature  at 
which  it  is  desired  to  dry  the 
substance.  If  a  substance  cannot 


FIG.  29. 


be  heated  it  is  best  dried  in  a  vacuum  desiccator  (Figs. 
30  and  31).  If  the  type  shown  in  Fig.  30  is  used,  one 
should  be  chosen  in  which  the  tap  is  in  the  side  and 
not  in  the  lid,  as  if  the  tap  is  in  the  lid  it  is  very  apt 
to  get  broken.  Hempel's  desiccator  (Fig.  31)  is  the 


FIG.  30. 


FIG.  31. 


more  rapid  in  its  action,  as  the  desiccating  substance 
is  placed  both  on  the  bottom  of  the  apparatus  and  in 
the  space  A. 

As  desiccating  substances,   concentrated  sulphuric 


20   PREPARATION  OF  ORGANIC  COMPOUNDS 

acid,  anhydrous  calcium  chloride,  soda-lime,  and  solid 
caustic  potash  or  caustic  soda  are  most  used.  If  the 
liquid  to  be  removed  is  an  acid,  such  as  acetic  acid,  a 
basic  desiccating  agent  such  as  potash  is  used,  whereas 
if  it  is  desired  to  remove  a  base,  such  as  pyridine,  the 
desiccator  is  charged  with  concentrated  sulphuric  acid. 
The  ground-glass  rim  of  the  desiccator  must  be  well 
greased  with  lard  or  vaseline.  Pure  vaseline  is  rather 
thin  for  the  purpose  and  can  be  advantageously  re- 
placed by  the  crude  article  (mineral  jelly).  When 
admitting  air  to  an  evacuated  desiccator,  the  tap  must 
be  opened  very  cautiously,  as  otherwise  the  dried 
substance  will  be  blown  about  and  lost. 

DRYING  LIQUIDS.  When  only  a  small  quantity  of 
a  liquid  is  to  be  dried,  it  is  best  first  to  dissolve  it  in 
some  neutral  solvent  such  as  ether,  ligroin,  benzene, 
&c.,  from  which  it  is  readily  separated  by  distillation, 
as  by  this  means  loss  is  avoided.  The  liquid  is  dried 
by  adding  a  dehydrating  agent  (anhydrous  calcium 
chloride,  potassium  carbonate,  sodium  sulphate,  caustic 
potash,  copper  sulphate,  &c.),  allowing  it  to  stand 
for  some  time,  and  then  filtering  and  distilling.  With 
the  exception  of  caustic  potash,  it  is  very  convenient 
to  add  the  finely  powdered  dehydrating  agent  slowly, 
shaking  well  after  each  addition.  Under  these  cir- 
cumstances, an  oily  layer  consisting  of  a  solution  of  the 
dehydrating  agent  in  the  water  present  first  separates. 
On  the  addition  of  more  dehydrating  agent  this  becomes 
very  viscous  and  adheres  to  the  sides  of  the  vessel,  so 
that  the  dried  liquid  can  be  poured  off  at  once.  This 
method  is  particularly  applicable  when  ethereal  solu- 
tions are  being  dried  with  calcium  chloride. 

In  preparing  absolute  ether,  sodium  should  be 
added,  and  the  whole  allowed  to  stand  until  no  more 
gas  is  given  off.  The  ether  is  then  decanted  and 
distilled  over  fresh  sodium. 

Alcohol  can  be  rendered  almost  anhydrous  by  dis- 
tilling over  burnt  lime.  The  last  traces  of  water  can 
then  be  removed  by  means  of  metallic  calcium. 

In  drying  aldehydes  and  ketones  it  must  be  borne 


APPARATUS,  METHODS,    REAGENTS 


l 


\ 


21 

in  mind  that  they  readily  undergo  the  aldol  conden- 
sation under  the  influence  of  dehydrating  agents. 

EXTRACTING  SOLIDS.  Solids 
are  best  extracted  in  a  Soxhlet 
apparatus  (Fig.  32).  The  sub- 
stance is  placed  in  the  thimble  of 
filter-paper  A,  the  top  of  which  is 
closed  with  a  very  loose  plug  of 
cotton-wool  or  glass-wool.  The 
liquid  is  boiled  in  the  flask  B,  the 
vapour  ascends  to  the  reflux-con- 
denser, and  the  condensed  liquid 
falls  into  the  thimble.  When  the 
level  of  the  liquid  reaches  c  it 
is  automatically  returned  to  the 
flask  by  the  siphon  D.  The  action 
of  the  apparatus  is  purely  mechani- 
cal, and  it  can  be  left  running  for 
hours  without  attention.  It  is  ad- 
visable to  tie  a  piece  of  asbestos 
paper  round  the  extractor  to  pre- 
vent undue  condensation  in  c. 
More  rapid  extraction  takes  place 
if  the  substance  is  mixed  with 
bits  of  broken  glass  before  being 
placed  in  the  thimble. 

EXTRACTING  LIQUIDS.  When 
a  substance  is  shaken  with  two 
liquids  in  which  it  is  soluble,  it 
divides  itself  between  the  two  sol- 
vents according  to  its  solubility 
in  each,  and  according  to  the 
amount  of  each  solvent  present. 
The  theory  of  this  will  be  found 
discussed  in  any  text-book  of  physical  chemistry. 
This  partition  of  a  substance  between  two  immiscible 
solvents  is  one  of  the  most  frequently  used  methods 
of  isolating  organic  preparations,  especially  for  removing 
ether-soluble  substances  from  aqueous  solutions.  The 
extraction  is  carried  out  simply  by  shaking  the  solution 


FIG.  32. 


22        PREPARATION  OF  ORGANIC  COMPOUNDS 

in   one   solvent   with   the   second   solvent    and    then 

separating  the  two  layers.     The  extraction  is  carried 

.  out  in  a  separating  funnel 

J    L  -   -,  (Figs.  33  and  34),  the  layers 

being  separated  by  drawing 
off  the  lower  one  by  means 
of  the  tap.  Both  forms  of 
apparatus  illustrated  are 
convenient ;  the  pear-shaped 
form,  however,  is  perhaps 
the  more  generally  useful,  as 
it  is  the  more  convenient 
shape  for  use  as  a  dropping 

FIG.  33.  FIG.  34.        funnel.    In  carrying  out  ex- 

tractions it  must  be  borne 
in  mind  that  it  is  more  effec- 
tive to  extract  several  times 
with  small  quantities  of  sol- 
vent than  to  extract  once 
with  a  large  quantity,  and 
that  the  less  soluble  the  sub- 
stance is  in  the  extracting 
liquid,  the  more  difficult  it 
will  be  to  extract.  It  some- 
times happens  that  an  emul- 
sion is  formed  which  does  not 
separate  into  two  layers  on 
standing.  "  Breaking  "  such 
emulsions  requires  some  expe- 
rience, but  it  can  often  be 
done  by  adding  more  of  one 
of  the  solvents.  Water-ether 
emulsions  are  usually  most 
readily  broken  by  adding  a 
little  alcohol.  The  addition 
of  calcium  chloride  and  of 
sodium  sulphate  is  also  some- 
times effective. 

DISTILLATION.     Distillation  at  atmospheric  pres- 
sure is  carried  out  from  an  ordinary  distilling  flask 


FIG.  35. 


APPARATUS,   METHODS,   REAGENTS  23 

(Fig.  35),  the  side-tube  being  connected  with  the 
condenser.  The  neck  of  the  flask  carries  a  thermo- 
meter, the  bulb  of  which  should  be  on  a  level  with  the 
side-tuba.  A  few  pieces  of  porous  pot  should  always  be 
added  to  prevent  bumping.  When  distillation  is  to 
be  carried  out  under  reduced  pressure,  a  Claisen 
flask  (Fig.  36)  is  most  suitable,  and  the  pear-shaped 
variety  is  more  convenient  than  the  round.  The  side- 
tube  is  connected  to  the  condenser,  and  the  neck  to 
which  it  is  sealed  carries  the  thermometer.  The  main 


FIG.  36. 

neck  of  the  flask  carries  a  glass  tube  drawn  out  to  a 
capillary  at  both  ends,  one  end  reaching  right  to  the 
bottom  of  the  flask.  By  this  means  a  slow  stream  of  air 
is  drawn  through  the  liquid  during  distillation,  and 
"bumping"  thereby  greatly  lessened.  t  By  carefully 
drawing  oif  the  top  capillary  the  flow  of  air  can  be  easily 
adjusted  during  the  distillation.  The  receiver  is 
connected  by  an  air-tight  joint  to  the  condenser,  and, 
if  only  one  fraction  is  to  be  collected,  may  consist  of 
an  ordinary  distilling  .flask,  the  side-tube  of  which  is 
connected  to  the  gauge  and  pump.  This  arrangement 
can  also  be  used  for  distillation  at  atmospheric  pressure 


24        PREPARATION  OF  ORGANIC  COMPOUNDS 

when  it  is  desired  to  protect  the  distillate  from  atmo- 
spheric moisture,  the  side-tube  in  this  case  being 
connected  with  a  calcium  chloride  tube. 

A  large  number  of  devices  have  been  proposed  from 
time  to  time  for  enabling  several  fractions  to  be  col- 
lected from  a  distillation  in  vacuo  without  destroying 

the  vacuum.  Of  these,  that 
illustrated  in  Fig.  37  is  by 
far  the  most  convenient. 
The  condenser  is  connected 
to  A  and  the  gauge  and 
pump  to  B.  The  tap  D  is 
closed,  c  and  E  opened,  and 
the  distillate  collected  in  F. 
When  it  is  desired  to 
change  the  receiver,  c  and 
E  are  closed  and  D  opened. 
The  receiver  F  is  then 
changed,  the  tap  D  closed, 
and  first  E,  and  then  after 
a  minute  c,  opened.  During 
these  operations  there  is  no 
need  to  interrupt  the  dis- 
tillation, as  the  distillate 
collects  in  G. 

In  carrying  out  distilla- 
FIG.  37.  tions  in  vacuo  the  burner 

should  be  held  in  the  hand 

and  continually  moved  about.  All  rubber  or  cork 
joints  should  be  made  air-tight  by  painting  them 
with  paraffin  wax,  or,  if  they  are  liable  to  become 
hot,  with  collodion,  after  the  apparatus  has  been 
exhausted.  With  a  good  head  of  water  there  should 
be  no  difficulty  in  carrying  out  distillations  at  10  to 
12  mm.  when  only  a  water -pump  is  used. 

Distillation  in  steam  is  frequently  resorted  to  as  a 
means  of  purifying  preparations.  The  amount  of 
substance  which  passes  over  depends  on  its  vapour 
pressure  at  100°  and  upon  its  molecular  weight.  The 
method  of  carrying  out  the  operation  is  obvious  from 


APPARATUS,  METHODS,  REAGENTS  25 

the  diagram  (Fig.  38).  The  sloping  position  of  the 
flask  is  adopted  in  order  to  avoid  splashing,  and  the  heat 
applied  to  the  flask  is  merely  to  prevent  undue  conden- 
sation. It  is  often  advantageous  to  employ  superheated 


FIG.  38. 

steam.  The  superheating  is  brought  about  by  interpos- 
ing a  copper  spiral  heated  by  a  Fletcher  burner,  or  a 
lead  spiral  heated  in  an  oil-bath,  between  the  boiler  and 
the  flask.  Steam  is  best  generated 
in  an  ordinary  tin-plate  can  pro- 
vided with  a  safety  tube  reaching 
to  the  bottom.  A  convenient 
arrangement  for  continuously  sepa- 
rating the  two  layers  is  shown  in 
Fig.  39.  The  condenser  is  con- 
nected to  A  and  the  heavier  layer 
drawn  off  from  time  to  time  at  B. 
The  lighter  layer  continuously 
flows  over  by  the  tube  c. 

Fractional  distillation  of  mix- 
tures of  liquids  whose  boiling-points 
lie  close  together  is  greatly  facili- 
tated by  using  a  column  appa- 
ratus. Numerous  forms  of  these 


FIG.  39. 


have  been  proposed,  three  of  which  are  shown  in  the 
illustration  (Fig.  40).  The  principle  on  which  they  are 
constructed  is  to  condense  the  less  volatile  portions 
and  cause  them  to  be  distilled  by  the  ascending 


26        PREPARATION  OF  ORGANIC  COMPOUNDS 

vapours.  Thus,  for  example,  the  least  volatile  portions 
will  condense  at  A.  The  drop  of  liquid  which  collects 
is  heated  by  the  ascending  vapours  when  the  more 
volatile  portions  evaporate  and  condense  at  B.  These 


at 


FIG.  40, 

are  in  turn  heated  by  the  vapours,  which,  however,  are 
somewhat  cooler  than  at  A,  and  lose  their  more  vola- 
tile portions,  which  condense  at  c,  and  so  on.  It  will 
thus  be  seen  that  by  the  time  the  vapours  reach  the 
condenser  they  have  undergone  several  distillations. 
In  systematic  fractionations  the  liquid  is  distilled 


APPARATUS,  METHODS,  REAGENTS  27 

so  that  the  distillate  collects  at  a  regular  speed  of 
about  two  drops  a  second,  the  receiver  being  changed 
about  every  5°.  The  first  fraction  is  then  redistilled 
until  the  temperature  has  risen,  say,  3°.  The  second 
fraction  is  then  added,  the  receiver  changed,  and  the 
distillate  collected  until  the  temperature  has  risen, 
say,  another  3°.  The  receiver  is  then  again  changed, 
the  third  fraction  added,  and  this  process  continued. 


FIG.  41. 


FIG. 42. 


The  whole  process  is  then  repeated  until  fractions 
with  constant  boiling-points  are  obtained.  The  tem- 
perature intervals  cited  above  are,  of  course,  merely 
illustrative,  the  intervals  actually  chosen  depending  on 
how  rapidly  the  boiling-point  of  the  mixture  rises. 

SUBLIMATION.  Solids  often  pass  into  the  gaseous 
state  without  melting,  and  when  this  is  the  case  sublima- 
tion frequently  affords  a  ready  means  of  purification. 
Substances  which  readily  condense  are  placed  in  a 
crucible  which  is  fixed  in  a  hole  in  a  sheet  of  asbestos, 
covered  with  a  bell-jar  or  large  conical  funnel,  and  the 
crucible  then  very  slowly  heated  (Fig.  41).  The 


i 


28        PREPARATION  OF  ORGANIC  COMPOUNDS 

sublimed  substance  condenses  on  the  sides  of  the  jar 
or  funnel. 

More  readily  volatile  substances  are  heated  in  a 
wide-necked  flask  on  a  sand- 
bath,  the  flask  being  provided 
with  a  tube  in  which  cold  water 
is  made  to  circulate  in  the  direc- 
tion shown  by  the  arrow-heads 
(Fig.  42).  The  sublimed  sub- 
stance condenses  on  the  cold 
surface  of  this  tube. 

To  sublime  a  substance  in 
vacuo  it  is  placed  in  a  tube 
provided  with  a  rubber  cork 
and  a  tap.  After  evacuation 
the  tap  is  closed,  the  tube 
immersed  to  about  half  its 
length  in  an  oil-  or  air-bath, 
and  heated.  The  sublimed  sub- 
stance condenses  in  the  cool, 
upper  part  of  the  tube. 

MELTING-POINTS.  Capillary 
tubes  about  3  in.  long  are  made 
by  drawing  out  thin-walled 
glass  tubing  and  cutting  the 
capillary  thus  formed  into  pieces 
of  the  required  length.  These 
are  sealed  at  one  end.  In  order 
to  determine  the  melting-point 
of  a  substance  it  is  carefully 
dried,  finely  powdered,  and  then 
a  little  of  it  shaken  down  to  the 
sealed  end  of  one  of  the  capil- 
laries. The  capillary  is  then 
attached  to  a  thermometer  by 
FIG  43  means  of  a  rubber  band  (made 

by  cutting  a  thin    slice   off    a 

piece  of  rubber  tubing)  in  such  a  way  that  the  sub- 
stance is  opposite  the  bulb  of  the  thermometer.  The 
bulb  is  then  immersed  in  concentrated  sulphuric 


APPARATUS,   METHODS,   REAGENTS  29 

acid  contained  in  a  small  flask  or  in  a  special  tube, 
as  shown  in  Fig.  43.  The  acid  is  then  heated 
until  the  substance  is  seen  to  melt,  the  whole  being 
well  stirred  by  moving  the  stirrer  A  up  and  down. 
This  stirrer  can  be  omitted  if  the  bath 
is  heated  slowly,  but  more  accurate 
figures  are  obtained  if  the  bath  is  well 
stirred.  The  use  of  a  P-tube  (Fig.  44) 


FIG.  44. 


FIG.  45. 


also  eliminates  the  use  of  the  stirrer,  the  heat  being 
applied  at  A.  These  tubes,  however,  are  very  apt  to 
break  at  high  temperatures. 

BOILING-POINTS.  These  are  best  determined  by 
distilling  a  portion  of  the  liquid  from  a  small  distilling 
flask.  If  sufficient  liquid  is  not  available  for  this,  it 


30   PREPARATION  OF  ORGANIC  COMPOUNDS 

is  placed  in  a  not  too  narrow  glass  tube  sealed  at  one 
end.  A  capillary  tube  sealed  at  the  upper  end  is 
dropped  in  and  the  whole  then  attached  to  the  ther- 
mometer (Fig.  45),  and  heated  as  described  in  the  above 
paragraph.  The  air  contained  in  the  capillary  tube 
expands  and  the  bubbles  passing  through  the  liquid 
prevent  superheating. 

REAGENTS 

Chemicals  of  technical  purity  are  quite  suitable  for 
carrying  out  preparations  and  are  a  great  deal  less 
expensive  than  pure  substances.  They  often  come 
on  to  the  market  in  lumps  and  are  best  ground  in  an 
ordinary  coffee-mill. 

Sulphuric  Acid.  Pure  sulphuric  acid  for  analysis  is 
a  distilled  acid.  Its  density  is  about  66°  Be',  and  it 
contains  96  to  98  per  cent,  of  H2SO4.  Monohydrate 
is  100  per  cent.  H2SO4,  and  is  prepared  by  adding  oleum 
to  a  more  dilute  acid  until  the  right  strength  is 
obtained.  The  commercial  article  is  often  quite 
opaque  owing  to  the  presence  of  flue-dust.  This, 
as  a  rule,  does  not  have  any  bad  effect,  but  if  desired 
can  be  removed  by  filtration  through  asbestos.  Oleum 
(fuming  sulphuric  acid)  can  be  obtained  of  any  strength, 
but  an  acid  containing  about  66  per  cent,  of  free  SO3  is 
most  suitable,  as  it  does  not  freeze  readily.  It  is 
diluted  down  to  the  required  strength  with  mono- 
hydrate. 

Hydrochloric  Acid.  Pure  concentrated  hydrochloric 
acid  contains  about  38  per  cent,  of  HC1.  For  organic 
preparations  it  can  in  almost  all  cases  be  replaced  by 
the  less  expensive  commercial  acid  (spirits  of  salt, 
Tower  salts).  This  is  coloured  yellow  by  the  presence 
of  iron  and  contains  from  25  to  30  per  cent.  HC1. 

Nitric  Acid.  The  ordinary  concentrated  nitric  acid 
has  a  density  of  1*4,  and  contains  63  per  cent,  of  HNO3. 
The  ordinary  fuming  nitric  acid  has  a  density  of  1-5 
and  contains  94  per  cent,  of  HNO3.  An  acid  of  density 
1-52  corresponding  to  997  per  cent.  HNO3  can  also 
be  purchased.  All  concentrated  nitric  acids  rapidly 


APPARATUS,  METHODS,  REAGENTS  31 

acquire  a  red  colour  owing  to  the  liberation  of  oxides 
of  nitrogen. 

Ammonia.  Concentrated  aqueous  ammonia  has  a 
density  of  O'88o  and  contains  about  35  per  cent,  of 
NH3.  Ammonia  gas  is  obtained  by  warming  this 
solution  and  drying  the  evolved  ammonia  by  passing 
it  over  quicklime  or  soda-lime.  It  is  more  convenient 
to  obtain  the  gas  from  a  cylinder  of  anhydrous,  liquid 
ammonia. 

Caustic  Soda.  Caustic  soda  containing  98  per  cent. 
NaOH  can  be  bought  in  powder  in  tins  and  is  more 
convenient  than  the  fused  sticks.  As  a  rule  it  is 
convenient  also  to  keep  the  commercial  solution. 
This  can  be  obtained  in  any  strength,  a  33  per  cent. 
solution  being  most  suitable  for  laboratory  purposes. 
Buying  the  commercial  solution  is  considerably  more 
economical  than  buying  the  solid  alkali  and  then 
dissolving  it  in  water. 

Anhydrous  Aluminium  Chloride.  It  is  usually  best 
to  buy  this  reagent,  the  most  satisfactory  brand  being 
that  sold  in  sealed  bottles  by  Kahlbaum.  If  desired, 
however,  it  can  be  prepared  by  passing  dry  chlorine 
over  aluminium  foil  packed  in  a  hard  glass  tube.  The 
reaction  is  started  by  warming  the  end  of  the  tube 
nearest  the  source  of  chlorine.  The  aluminium 
chloride  sublimes  and  is  collected  in  a  flask  provided 
with  a  calcium  chloride  tube  to  exclude  atmospheric 
moisture. 

Cuprous  Chloride.  Cuprous  chloride  can  be  bought 
at  a  reasonable  price,  or  it  can  be  prepared  by  one  of  the 
two  following  methods : 

(a)  l  Cupric  chloride  is  dissolved  in  boiling  water 
and  the  calculated  quantity  of  copper  powder  (Natur- 
kupfer  C)  slowly  added  to  the  boiling  solution.     At 
the  end  of  two  or  three  minutes  the  solution  will 
have    become    completely    colourless.     The    cuprous 
chloride  is  then  filtered  off  as  rapidly  as  possible,  and 
dried  out  of  contact  with  the  air. 

(b)  Two  hundred  and  fifty  grammes  of  crystallised 

1  B.  29,  1878. 


32        PREPARATION  OF  ORGANIC  COMPOUNDS 

copper  sulphate,  120  grm.  of  common  salt,  and  500  c.c. 
of  water  are  heated  to  boiling.  One  kilogramme  of 
concentrated  hydrochloric  acid  and  130  grm.  of  copper 
turnings  are  added,  and  the  whole  gently  boiled  until 
decolorised,  oxidation  by  the  air  being  avoided  as  far 
as  possible  by  closing  the  mouth  of  the  flask  with  a 
loose  plug  of  glass-wool.  The  solution  is  rapidly 
poured  off  from  unchanged  copper  and  then  well- 
boiled  water  added  until 
no  more  cuprous  chloride 
is  precipitated.  As  cu- 
prous chloride  is  most  fre- 
quently used  in  solution 
in  hydrochloric  acid,  e.g. 
in  carrying  out  Sand- 
meyer's  reaction  (p.  75), 
it  is  convenient  not  to 
precipitate  it,  but  to  weigh 
the  solution  poured  off 
from  the  excess  of  copper 
and  then  to  dilute  it  with 
concentrated  hydrochloric 
acid  until  the  total  weight 
is  2036  grm.  The  result- 
ing solution  contains  about 
10  per  cent,  of  Cu2Cl2. 
Cuprous  Bromide.  Cuprous  bromide  is  obtained  by 
boiling  125  grm.  of  crystallised  copper  sulphate  with 
360  grm.  of  potassium  bromide,  800  c.c.  of  water,  200 
grm.  of  copper  turnings,  and  no  grm.  of  concentrated 
sulphuric  acid  until  the  whole  is  decolorised. 

Sodium.  Oil  should  be  removed  from  the  surface 
of  the  sodium  by  means  of  dry  blotting  paper,  and  the 
metal  then  cut  into  thin  slices  or  pressed  into  wire 
by  means  of  a  sodium  press  (Fig.  46).  After  use  the 
die  should  be  at  once  removed  and  placed  in  alcohol. 
It  should  not  be  thrown  into  water,  as  if  this  is  done 
any  sodium  adhering  to  the  inside  may  give  rise  to  an 
explosion.  Granulated  sodium  is  obtained  as  follows.1 
i  B.  21,  1464;  35,  3516;  J.  pr.  [2]  54,  116. 


FIG.  46. 


APPARATUS,  METHODS,  REAGENTS  33 

The  metal  is  covered  with  a  fairly  deep  layer  of  dry 
paraffin  or  xylol  and  heated  to  120°.  The  flask 
is  then  corked,  wrapped  up  in  a  thick  cloth,  and 
well  shaken  for  a  minute  or  two.  The  metal  is  thus 
obtained  in  the  form  of  a  powder.  Quantities  up  to 
about  50  grm.  can  be  safely  dealt  with  in  one  operation. 
The  paraffin  or  xylol  can  then  be  replaced  by  any  desired 
neutral  solvent,  such  as  anhydrous  ether,  ligroin,  &c., 
by  washing  several  times  by  decantation. 

Sodium  Ethoxide.  An  alcoholic  solution  of  sodium 
ethoxide  is  very  readily  obtained  by  slowly  adding 
thin  strips  of  sodium  to  excess  of  absolute  alcohol. 
The  heat  given  out  during  the  reaction  causes  the  alcohol 
to  boil,  and  the  preparation  should,  therefore,  be  carried 
out  under  a  reflux  condenser.  In  order  to  isolate 
the  solid  ethoxide  free  from  alcohol,  the  alcoholic 
solution  must  be  distilled  in  a  current  of  hydrogen 
from  a  copper  retort,  the  last  traces  of  alcohol  not  being 
lost  below  200°.  When  the  dry  product  is  required  it 
is  best  to  prepare  sodium  powder  as  fine  as  possible 
by  the  method  given  above,  using  250  c.c.  of  xylol, 
&c.,  to  each  23  grm.  of  sodium.  The  xylol  and  sodium 
are  then  placed  in  a  flask  provided  with  a  reflux 
condenser  and  agitator,  cooled  with  ice,  and  the 
calculated  quantity  of  alcohol,  diluted  with  two  volumes 
of  xylol,  &c.,  added  slowly.  When  all  the  alcohol  has 
been  added,  and  the  violent  reaction  has  subsided, 
the  whole  is  heated  gently  on  the  water-bath  for  a  time 
in  order  to  complete  the  reaction.  The  ethoxide  thus 
obtained  forms  a  snow-white,  flocculent  precipitate 
which  shows  greater  reactivity  than  that  prepared 
by  other  methods. 

TEST-PAPERS.  Litmus  paper  is  affected  by  both 
inorganic  and  organic  acids,  and  can  usually  be 
conveniently  replaced  by  Congo  paper.  This  is  pre- 
pared by  steeping  filter -paper  in  a  solution  prepared 
by  dissolving  3  grm.  of  Congo  red  in  a  litre  of  boiling 
water  to  which  a  few  drops  of  sodium  carbonate  have 
been  added.  It  is  turned  blue  by  inorganic  acids 
and  brown  by  organic  acids.  The  blue  colour  is, 

3 


34        PREPARATION  OF  ORGANIC  COMPOUNDS 

however,  also  produced  by  concentrated  organic 
acids. 

Alkalis  are  best  detected  by  Brilliant  Yellow  paper. 
This  is  prepared  by  steeping  filter-paper  in  a  solution  of 
1-5  grm.  of  Brilliant  yellow  in  1000  c.c.  of  boiling  water 
containing  two  or  three  drops  of  acetic  acid.  It  is 
turned  red  by  caustic  alkalis,  alkali  carbonates,  and 
ammonia. 

Nitrous  acid  is  detected  by  means  of  starch-iodide 
paper.  To  prepare  this,  10  grm.  of  starch  are  ground  to 
a  thin  cream  with  cold  water  and  then  poured  slowly 
into  one  litre  of  boiling  water.  The  whole  is  boiled  for 
two  to  three  minutes  and  then  cooled  as  rapidly  as 
possible.  When  cold  a  solution  of  3-5  grm.  of  potassium 
iodide  is  added.  Filter-paper  is  steeped  in  the  solution 
thus  obtained,  and  dried  in  as  clean  an  atmosphere 
as  possible.  It  should  be  preserved  in  well-stoppered 
bottles,  and  if  properly  prepared  should  give  a  pure 
blue  colour  with  nitrous  acid  and  other  oxidising 
agents. 


CHAPTER  II 
THE  HYDROCARBONS 

IN  this  chapter  no  attempt  can  be  made  to  mention 
all  the  methods  employed  in  the  preparation  of  hydro- 
carbons, but  the  most  important  reactions  will  be 
discussed  briefly.  It  should  be  pointed  out  that 
the  artificial  preparation  of  hydrocarbons  is  in 
most  cases  of  theoretical  rather  than  practical  im- 
portance, the  majority  of  important  hydrocarbons 
being  obtained  from  natural  sources,  viz.  petroleum 
(paraffin),  coal  tar  (benzene  and  its  homologues, 
naphthalene  and  anthracene),  and  turpentine  oil 
(terpenes).  The  most  important  synthetic  hydro- 
carbon is  acetylene,  obtained  by  the  action  of  water 
on  calcium  carbide,  and  is  too  well  known  to  require 
further  mention. 

FROM  THE  HALOGEN  COMPOUNDS.  Hydro- 
carbons can  be  obtained  from  the  halogen  compounds 
by  three  methods,  viz.  : 

(a)  Retrogressive  Substitution.  This  consists  in 
replacing  the  halogen  atom  by  one  of  hydrogen  and  is 
usually  accomplished  by  heating  (under  pressure  if 
necessary)  with  concentrated  hydriodic  acid  and  red 
phosphorus.  The  method  is  often  useful  for  reducing 
alcohols,  aldehydes,  and  ketones,  the  hydroxyl  group, 
or  aldehydic  or  ketonic  oxygen  atom  having  been 
previously  replaced  by  halogen. 

(6)  Action  of  Metals.  This  method  was  originally 
proposed  by  Wiirtz  for  the  synthesis  of  the  paraffins 
by  treating  the  alkyl  halides  with  metallic  sodium,  and 
was  extended  to  the  aromatic  series  by  Fittig.  The 

35 


36        PREPARATION  OF  ORGANIC  COMPOUNDS 

reaction  consists  in  the  removal  of  the  halogen   as 
sodium  halide  and  union  of  the  two  radicals  : 

2RHlg  +  2Na  =  R  -  R  +  aNaHlg. 

The  synthesis  can  be  varied  by  employing  a  mixture 
of  two  halides,  e.g.  bromobenzene  and  ethyl  bromide, 
when  treated  with  sodium,  give  ethyl  benzene. 

The  reaction  is  carried  out  by  heating  the  halogen 
compounds  with  rather  more  than  the  calculated 
quantity  of  sodium  in  the  form  of  thin  slices,  wire,  or 
powder  (p.  32)  in  some  neutral  solvent,  such  as  ether, 
ligroin,  benzene,  &c.  In  some  cases,  however,  the 
reaction  is  best  carried  out  without  a  solvent  (see 
sy  m.  -diphenyl  ethane,  below) .  Also  recent  experiments 
made  by  the  author  point  to  liquid  ammonia  (in  which 
sodium  dissolves  to  give  a  deep  blue  solution)  being  a 
useful  solvent  in  some  cases. 

PREPARATION  OF  ETHYL  BENZENE  (C6H5 .  C2Hs)  .1 
Fifty  grammes  of  bromobenzene  and  45  grm.  of  ethyl  bromide 
are  dissolved  in  about  100  c.c.  of  anhydrous  ether,  and  25  grm. 
of  sodium  in  thin  slices  or  as  wire  added  through  a  reflux 
condenser,  the  flask  being  cooled  with  ice.  The  whole  is  allowed 
to  stand  over-night  and  the  supernatant  liquid  then  decanted 
from  the  sodium  bromide  and  unchanged  sodium.  Owing  to 
the  presence  of  this  latter  the  residue  must  be  destroyed 
by  adding  it  little  by  little  to  cold  water.  The  ethyl  benzene 
is  isolated  from  the  ethereal  solution  by  fractional  distillation. 
It  forms  a  colourless  liquid  boiling  at  134°.  The  yield  is  about 
60  per  cent. 

PREPARATION  OF  syw.-DIPHENYL  ETHANE  (Dibenzyl) 
(C6H5.CH2.CH2.C6H5).2  A  slight  excess  of  sodium  is  added 
to  benzyl  chloride  (12  parts  sodium,  50  parts  benzyl  chloride) 
alone  or  dissolved  in  two  volumes  of  dry  toluene,  and  the 
whole  heated  under  a  reflux  condenser  on  the  water-bath 
until  no  further  change  takes  place.  If  no  toluene  has 
been  added  the  whole  is  extracted  with  anhydrous  ether  and 
the  ethereal  extract  fractionated.  If  the  reaction  has  been 
carried  out  in  the  presence  of  toluene,  the  toluene  solution 

1  A.  131,  303,  310.  2  A.  121,  250  ;    137,  258. 


THE  HYDROCARBONS  37 

is  poured  off,  the  residue  washed  once  or  twice  by  decantation 
with  toluene,  and  the  united  liquors  then  fractionated.  The 
dibenzyl  is  finally  recrystallised  from  alcohol.  Colourless 
needles  melting  at  5i°-52°  and  boiling  at  248°. 

A  large  number  of  symmetrical  diphenyl  derivatives 
have  been  prepared  by  heating  aromatic  halogen 
compounds  with  copper  powder.1  The  reaction  is  a 
very  general  one  so  far  as  the  iodo-compounds  are 
concerned,  but  the  chloro-  and  bromo-compounds  only 
react  when  nitro-groups  are  present  in  the  ortho-  or 
para-positions.  Thus  o-  and  ^-nitrobromobenzene 
give  2.2'  and  44'-dinitrodiphenyl  in  good  yield,  whereas 
3.3'-dinitrodiphenyl  can  only  be  obtained  from  w.-nitro- 
iodobenzene.  The  reaction  is  carried  out  by  heating 
the  iodo-compound  with  about  its  own  weight  of  copper 
powder  to  a  temperature  of  230°  to  280°,  and  hence 
it  is  frequently  necessary  to  work  in  closed  vessels. 
The  reaction  takes  place  a  great  deal  more  readily  when 
nitro-groups  are  present  in  the  ortho-  or  ^)«ra-positions. 
Thus  2.4-dinitro-i-chlorobenzene  is  converted  into  the 
corresponding  diphenyl  derivative  by  boiling  with 
copper  powder  in  nitrobenzene  solution.  The  yields 
are  usually  60  to  80  per  cent. 

PREPARATION  OF  DIPHENYL  (CaH5.C6H5).  Twenty 
grammes  of  iodobenzene  and  20  grm.  of  copper  powder  are 
heated  for  three  hours  in  a  sealed  tube  to  230°.  The  contents 
of  the  tube  are  then  extracted  with  ether,  and  the  ethereal 
extract  filtered  and  fractionated.  The  diphenyl  (B.P.  250°- 
255°)  is  finally  purified  by  recrystallisation  from  alcohol. 
Colourless  leaflets  melting  at  /o0-?!0.  The  yield  is  82  per 
cent. 

PREPARATION    OF    2.4.2'.  4'-TETRANITRODIPHENYL 

(N02)2[2.4]C6H3[i.i/]C6H3(N02)2[2/.4/].2  .  Ten  grammes  2.4- 
dinitro-chlorobenzene  and  10  grm.  of  copper  powder  are 
boiled  for  an  hour  under  a  reflux  condenser  with  20  c.c.  of 
nitrobenzene.  After  cooling,  the  solution  is  diluted  with 
ether,  filtered,  and  ligroin  slowly  added  to  the  filtrate.  An 
oil  separates  which  becomes  crystalline  when  the  vessel  is 

i  B.  34,  2176.  2  B.  34,  2177. 


38        PREPARATION  OF  ORGANIC  COMPOUNDS 

scratched.  It  is  collected  and  recrystallised  from  benzene. 
Yellowish  prisms  melting  at  163°.  The  yield  is  66  per  cent. 

(c)  By  the  Loss  of  Halogen  Acid.  This  method  gives 
rise  to  unsaturated  compounds  : 

-CH2-CHHlg-  -CH  =  CH-  +  HHlg 

and  has  proved  particularly  useful  in  the  study  of  the 
terpenes.  The  reaction  is  carried  out  by  heating  the 
halogen  compound  with  alcoholic  (best  methyl  alco- 
holic) caustic  potash,  with  alkali  phenolates,  or  with 
organic  bases  such  as  aniline,  dimethylaniline,  quino- 
line,1  &c. 

PREPARATION  OF  MENTHENE  (C10H18).2  One  hundred 
grammes  of  phosphorus  pentachloride  are  covered  with  dry 
petroleum  ether  and  100  grm.  of  menthol  added  little  by 
little,  the  whole  being  cooled  with  ice,  and  care  being  taken 
not  to  add  further  portions  of  menthol  until  no  more  hydro- 
chloric acid  is  evolved.  The  petroleum  ether  is  then  distilled 
off  and  the  residue  fractionated,  the  menthyl  chloride  (about 
70  grm.)  being  collected  at  2O5°-2i5°.  This  is  added  to  a 
hot  solution  of  75  grm.  of  caustic  potash  in  320  grm.  of  phenol, 
the  whole  heated  to  150°  for  ten  to  twelve  minutes  and  then 
distilled  until  a  thermometer  immersed  in  the  liquid  registers 
200°.  The  distillate  is  washed  with  aqueous  caustic  potash  until 
free  from  phenol  and  then  distilled  over  metallic  sodium. 
Colourless  liquid  boiling  at  i6o°-i66°.  The  rather  indefinite 
boiling-point  is  due  to  the  substance  not  being  quite  pure. 

CH(CH3)2  CH(CH3)2  CH(CH3)2 

I  I  I 

CH  CH  C 

/    \  /    \  S\ 

CHOHCH2  CH.C1CH2  CH     CH2 

I  '-II  II 

CH2       CH2  CH2       CH2  CH2    CH2 


CH  CH  CH 

I  I  I 

CH3  CH3  CH3 

Menthol  Menthyl  chloride  Menthene 

1  A.  227,  286  ;   245,  196  ;  B.  40,  603  ;  Soc.  85,  1403. 

2  B.  29,  1843  ;   25,  686. 


THE  HYDROCARBONS  39 

PREPARATION  OF  DIPENTENE  ([d  +1]  Limonene).i 
(C10H16).  Ten  grammes  of  dipentene  dihydrochloride  and 
20  grm.  of  aniline  are  cautiously  warmed  until  a  reaction  sets 
in,  and  the  heating  then  continued  for  two  or  three  minutes. 
Glacial  acetic  acid  (20  c.c.)  is  then  added  and  the  whole 
steam-distilled.  The  distillate  is  next  steam-distilled  with 
oxalic  acid  (mineral  acids  must  not  be  used),  and  this  process 
repeated  until  no  more  aniline  comes  over.  The  hydrocarbon 
is  separated  from  the  aqueous  portion  of  the  distillate,  dried 
over  solid  caustic  potash,  and  finally  distilled  over  sodium. 
It  forms  a  colourless  liquid  boiling  at  178°-! 80°. 

CH3     CH3  CH2     CH3 

NX 

c.ci 


CH,     CH2  CH     CH2 

NX  \/ 

C.CI  C 


C 


Dipentene  dihydrochloride  Dipentene 

FROM  THE  ALCOHOLS.  Hydrocarbons  can  be 
obtained  from  alcohols  by  two  methods  ; 

(a)  By  Loss  of  Water.  This  gives  rise  to  unsaturated 
compounds,  e.g.  : 

CH3.CH2OH  =  CH2 :  CH2  +  H2O. 

The  preparation  of  pyruvic  acid  by  heating  tartaric 
acid  with  acid  potassium  sulphate  (p.  125)  : 

f'HiCOH.COOH  COH.COOH     CO.COOH 

j  |  —      II  -|  +  H20  +  C02 

iHOJ  CH .  jCOOjH  CH2  CH3 

Enolic  form      Ketonic  form 
Tartaric  acid  Pyruvic  acid 

1  B.  40,  603  ;   A.  245,  196;  350,  150. 


40        PREPARATION  OF  ORGANIC  COMPOUNDS 

and  of  acrolein  by  heating  glycerine  with  potassium 
bisulphate  1  : 

['HO|CH2  CH2  CH2 


I      Hi  <-  iOHi     _*     2H2O  +  C          =  CH 

"II  II  /OH  | 

HO.HCjH    !  C<  CHO 


Enolic  Ketonic 

Acrolein 

are  the  best-known  examples  of  this  reaction.  The 
reaction  is  also  frequently  carried  out  by  heating  the 
alcohol  with  sulphuric  acid,  zinc  chloride,  phosphoric 
acid,  &c.  The  last-named  substance  has  the  advantage 
over  sulphuric  acid  that  no  sulphur  dioxide  is 
formed. 

PREPARATION  OF  ETHYLENE  (CH2  :  CH2).  (a)  A 
mixture  of  25  grm.  of  alcohol  and  150  grm.  of  concentrated 
sulphuric  acid  is  placed  in  a  capacious  flask  together  with 
some  dry  sand  (to  lessen  frothing),  and  the  whole  heated 
on  a  sand-bath  until  a  steady  stream  of  gas  is  evolved.  A 
mixture  of  100  grm.  of  alcohol  and  200  grm.  of  concentrated 
sulphuric  acid  is  then  slowly  run  in  from  a  dropping  funnel, 
the  end  of  which  should  be  drawn  out  to  a  point.  The  evolved 
gas  is  led  off  through  a  delivery  tube  in  the  usual  way  and  is 
freed  from  carbon  dioxide  and  sulphurous  acid  by  passing 
it  through  caustic  potash  solution.  It  is  finally  dried  by 
passing  through  concentrated  sulphuric  acid.  The  gas  can 
only  be  liquefied  by  means  of  liquid  air. 

(b)  2  About  50  c.c.  of  syrupy  orthophosphoric  acid  (D  = 
i -75)  are  heated  to  2OO°-22O°  (thermometer  bulb  in  liquid) 
and  maintained  at  this  temperature  while  alcohol  is  run  in 
very  slowly  by  means  of  a  dropping  funnel  drawn  out  to  a 
point  and  reaching  right  to  the  bottom  of  the  flask.  The 
gas  is  dried  by  passing  through  concentrated  sulphuric 
acid.  This  is  the  best  method  of  preparing  ethylene,  and 
is  recommended  for  use  in  the  preparation  of  ethylene  di- 
bromide  (p.  62). 

1  B.  20,  3388. 

2  Proc.  17,  147  ;  J.R.C.S.  32,  76  ;  C.  1900  L,  noi. 


THE  HYDROCARBONS  41 

Camphene  and  menthene  are  obtained  in  90  per  cent. 
yield  when  borneol  and  menthol  are  heated  on  the 
water-bath  for  six  to  eight  hours  with  continual  stirring 
with  dilute  sulphuric  acid  (i  acid,  2  water). 

(b)  By  Reduction.  The  alcohols  as  a  rule  are  best 
reduced  by  prolonged  heating  under  pressure  with 
concentrated  hydriodic  acid  and  red  phosphorus. 
Primary  and  secondary  alcohols  of  the  type  ArCH2OH 
can  be  reduced  by  sodium  and  alcohol,  the  hydrocarbon 
ArCH3  being  the  sole  product.  Alcohols  of  the  type 
ArCH :  CHOH  are  only  partially  reduced  by  this 
reagent,  a  mixture  of  ArCH2CH3  and  ArCH2.CH2OH 
being  produced,  the  latter  only  being  capable  of  reduc- 
tion by  treatment  with  hydriodic  acid.  The  tertiary 
alcohols,  including  the  phenols,  can  be  reduced  by 
distillation  over  hot  zinc-dust.  The  triaryl  carbinols, 
Ar3COH,  are  particularly  easily  reduced,  boiling  with 
glacial  acetic  acid  and  zinc  being  sufficient  treat- 
ment.1 

FROM  THE  ALDEHYDES  AND  KETONES. 
Both  classes  of  substances  on  exhaustive  reduction 
give  the  corresponding  hydrocarbon,  but  the  aldehydes 
are  best  first  converted  into  the  dichlor-compounds 
by  the  action  of  phosphorus  pentachloride,  and  these 
then  reduced  by  the  methods  cited  on  p.  35  : 

R.CHO    ->    R.CHC12    -    RCH3. 

This  procedure  is  also  best  when  it  is  desired  to  reduce 
a  fatty  ketone. 

The  mixed  aliphatic-aromatic  ketones  are  smoothly 
reduced  by  passing  their  vapour  mixed  with  hydrogen 
over  finely  divided  nickel  (prepared  by  reducing  nickel 
oxide  with  hydrogen  at  a  low  temperature)  at  a 
temperature  of  190°  to  195°. 

The  aromatic  ketones  are  readily  reduced  by  sodium 
(i  part)  and  boiling  alcohol  (10  parts). 

PREPARATION  OF  DIPHENYL  METHANE  (C6H6)2CH2.2 
Twenty  grammes  of  benzophenone  are  boiled  under  a  reflux 

1  B-  35.  3137  ;  M.  22,  613.  2  B.  31,  999- 


42        PREPARATION  OF  ORGANIC  COMPOUNDS 

condenser  with  200  grm.  of  alcohol;  and  20  grm.  of  metallic 
sodium  slowly  added  to  the  boiling  solution.  When  all  the 
sodium  has  dissolved,  the  contents  of  the  flask  are  satu- 
rated with  CO2  and  then  poured  into  cold  water  and  the  whole 
extracted  with  benzene.  The  benzene  solution  is  dried  over 
calcium  chloride,  the  benzene  distilled  off  from  the  water-bath, 
and  the  distillation  then  carried  on  under  reduced  pressure. 
The  diphenyl  methane  passes  over  at  174°-: 76°  at  80  mm. 
and  solidifies  in  the  receiver  to  a  mass  of  colourless  needles 
melting  at  25°-26°.  The  yield  is  about  90  per  cent. 

The  quinones  are  best  reduced  by  dry  distillation 
with  zinc  dust  (10  to  50  parts). 

FROM  UNSATURATED  COMPOUNDS.  Ethylenic 
bonds  can  be  saturated  by  heating  the  substance  in  an 
atmosphere  of  hydrogen  in  the  presence  of  a  contact 
substance  such  as  platinum-black  or  finely  divided 
nickel.  Palladium  and  its  hydroxide  also  act  as  hydro- 
gen carriers  and  their  use  has  been  suggested  as  a 
commercial  method x  of  reducing  the  unsaturated  fatty 
acids  obtained  from  Soya  bean  oil,  fish  oils,  &c.  (oleic 
acid,  linolic  acid,  &c.),  thus  rendering  it  possible  to 
obtain  a  hard  soap  from  these  fats. 

Ethylenic  bonds  can  also  be  reduced  by  sodium  and 
alcohol  or  by  sodium  amalgam.2 

THE  FRIEDEL-CRAFTS  REACTION.  This  is  one 
of  the  most  generally  known  methods  of  obtaining 
aromatic  hydrocarbons  and  consists  in  condensing 
the  alkyl  halide  with  an  aromatic  hydrocarbon  in 
the  presence  of  anhydrous  aluminium  chloride,  e.g.  : 

C6H6  +  RHlg  =  C6H5.R  +  HHlg. 

The  reaction  is  not  limited  to  alkyl  halides,  acyl  halides 
reacting  in  exactly  the  same  way  to  produce  ketones 
(p.  127). 

The  reaction  is  carried  out  either  by  mixing  the 
hydrocarbon  with  the  alkyl  halide  and  then  slowly 
adding  the  aluminium  chloride,  or  the  aluminium 
chloride  is  mixed  with  the  hydrocarbon  and  the  alkyl 
halide  slowly  added.  The  reaction  as  a  rule  takes 

1  E.P.  5188".  2  A.  121,  375. 


THE  HYDROCARBONS  43 

place  without  the  application  of  heat.  The  product 
is  finally  isolated  by  pouring  the  reaction  mixture 
into  water,  separating,  and  fractionating  the  product. 
As  a  rule  a  large  excess  of  the  hydrocarbon  is  used 
in  order  to  moderate  the  reaction,  but  this  effect  can 
also  be  brought  about  by  the  use  of  some  neutral 
solvent  such  as  ligroin,  carbon  bisulphide,  or  nitro- 
benzene. The  last  of  these  substances  is  often  espe- 
cially useful  owing  to  its  power  of  dissolving  anhydrous 
aluminium  chloride. 

The  action  of  the  aluminium  chloride  is  catalytic,  a 
small  quantity  being,  as  a  rule,  capable  of  converting 
a  large  quantity  of  hydrocarbon  into  its  homologue. 
In  the  case  of  ketones,  however,  the  aluminium 
chloride  often  forms  a  compound,  and,  therefore,  in 
condensing  an  acid  chloride  with  an  aromatic  compound 
it  is  usually  necessary  to  use  a  molecular  quantity  of 
aluminium  chloride. 

Aluminium  chloride  can  often  be  advantageously 
replaced  by  aluminium  foil  and  anhydrous  hydro- 
chloric acid  gas *  or  mercuric  chloride,  by  aluminium 
mercury  couple,2  or  by  anhydrous  ferric  chloride. 

PREPARATION  OF  TRIPHENYL  METHANE, 
(C6H5)3CH.3  Forty  grammes  of  chloroform,  previously  dried 
with  calcium  chloride,  are  dissolved  in  200  grm.  of  dry  benzene, 
the  whole  placed  in  a  flask  fitted  with  a  reflux  condenser, 
and  25  grm.  of  anhydrous  aluminium  chloride  added  little  by 
little.  The  reaction  sets  in  at  the  ordinary  temperature, 
causing  brisk  ebullition  and  evolution  of  hydrochloric  acid. 
When  all  the  aluminium  chloride  has  been  added  the  whole  is 
boiled  for  forty  minutes,  cooled,  and  then  poured  slowly  into 
cold  water.  The  benzene  layer  is  separated,  dried  over 
calcium  chloride,  and  then  distilled  at  the  ordinary  pressure 
until  the  temperature  reaches  200°.  The  residue  is  then 
fractionated  under  reduced  pressure.  Some  diphenyl  methane 
(B.P.  175°  at  80  mm.)  first  passes  over,  and  then  the  triphenyl 
compound.  The  distillation  is  continued  as  long  as  the 

1  B.  28,  1136. 

2  Soc.  67,  826. 

3  B.  26,  1961  ;  A.  235,  207. 


44        PREPARATION  OF  ORGANIC  COMPOUNDS 

distillate  solidifies  on  cooling.  The  hydrocarbon  is  then 
recrystallised  twice  from  benzene,  from  which  it  separates 
with  one  molecule  of  benzene  of  crystallisation.  This  benzene 
is  driven  off  by  heating  on  the  water-bath,  and  the  pure 
hydrocarbon  recrystallised  from  alcohol.  It  forms  colourless 
plates  melting  at  92°  and  boiling  at  358°.  The  yield  is  about 
35  per  cent. 

PREPARATION  OF  DIPHENYL  METHANE  (C6H5)2CH2.i 
One  gramme  of  aluminium  foil  in  thin  strips  is  treated  for 
one  to  two  minutes  with  a  concentrated  solution  of  mercuric 
chloride  and  then  rinsed  thoroughly,  first  with  cold  water, 
then  with  absolute  alcohol,  and  finally  with  benzene.  These 
operations  must  be  carried  out  as  rapidly  as  possible,  and  the 
couple  at  once  added  to  65  grm.  of  benzene  contained  in  a 
flask  fitted  with  a  reflux  condenser.  Thirty  grammes  of  benzyl 
chloride  are  then  slowly  run  in  during  an  hour,  when  a  brisk 
reaction  sets  in  with  rise  of  temperature  and  evolution  of 
hydrochloric  acid.  When  all  the  benzyl  chloride  has  been 
added,  the  whole  is  boiled  on  the  water-bath  for  fifteen  minutes, 
cooled,  shaken  up  with  dilute  caustic  soda,  and  the  benzene 
layer  separated.  The  aqueous  portion  is  extracted  with 
benzene,  the  benzene  solutions  united,  dried  over  calcium 
chloride,  and  the  benzene  then  removed  by  distillation  from 
the  water-bath.  The  residue  is  then  fractionated  under  reduced 
pressure,  the  diphenyl  methane  passing  over  at  174°-!  76°  at 
80  mm.  Colourless  needles,  M.P.  25°,  B.P.  262°.  The  yield 
is  about  20  per  cent. 

FROM  THE  DIAZO-COMPOUNDS.  This  method 
is  limited  to  the  aromatic  series,  and  can  be  carried  out 
in  two  directions,  viz.  : 

(a)  The  diazo-group  is  replaced  by  hydrogen.  The 
classical  method  of  reducing  a  diazo-compound  is  by 
heating  it  with  alcohol  : 

R.N  :  N.C1  -j-C2H5OH  = 

RH  +  N2  +  HC1  +  CH3CHO 

but    the    phenolic    ether    is    often    obtained    simul- 
taneously : 

R.N2C1  +  C2H6OH  =  R.OC2H5  +  N2  +  HCL 
i  Soc.  67,  826. 


THE  HYDROCARBONS  45 

Hypophosphorous  acid,  HPO2,  often  gives  excellent 
results.  It  is  applied  either  in  the  form  of  the  com- 
mercial solution  (D  =  1-15)  or  as  the  calcium  salt 
with  the  calculated  quantity  of  sulphuric  acid.  The 
diazo-compounds  can  also  be  reduced  by  sodium 
stannite 1  or  alkaline  solutions  of  sodium  hydro- 
sulphite,2  but  the  yields  are  usually  poor. 

Those  diazo-compounds  which  contain  negative 
groups  in  the  ortho-  or  ^am-position  usually  give  the 
best  yields  on  reduction. 

PREPARATION  OF  DIPHENYL  (C6H5 .  C6H5)  .3  Thirty 
grammes  of  benzidine  are  dissolved  in  70  grm.  of  concentrated 
hydrochloric  acid  and  400  c.c.  of  water,  and  diazotised  in  the 
usual  way  (see  p.  238)  with  sodium  nitrite  (23  grm.) .  A  filtered, 
ice-cold  solution  of  hypophosphorous  acid,  obtained  by  digest- 
ing 150  grm.  of  finely  powdered  calcium  hypophosphite  with 
45  c.c.  of  concentrated  sulphuric  acid  and  500  c.c.  of  water 
for  some  time  at  80°  or  a  corresponding  amount  of  the  com- 
mercial acid,  is  then  added  and  the  whole  allowed  to  stand  in 
the  ice-chest  for  several  days  until  no  more  solid  separates. 
The  diphenyl  is  then  filtered  off,  suspended  in  dilute  caustic 
soda,  and  distilled  in  steam.  M.P.  71°,  B.P.  254°.  The  yield 
is  60  per  cent. 

(b)  The  diazo-group  is  eliminated  and  two  aryl 
groups  linked  together.  This  method  is  confined  to 
the  preparation  of  symmetrical  diaryl  compounds.  The 
reaction  is  carried  out  either  by  adding  a  hydrochloric 
acid  solution  of  cuprous  chloride  to  the  diazo-salt,4 
in  which  case  part  of  the  diazo-compound  is  simul- 
taneously converted  into  the  corresponding  chloro- 
derivative  (Sandmeyer's  reaction,  see  p.  75),  or  the 
diazo-chloride  is  treated  with  copper  powder  5  (best, 
the  copper  paste  described  on  p.  75).  The  latter 
reaction  proceeds  most  smoothly  in  alcoholic  or  aqueous 
alcoholic  solution.  The  copper  powder  can  be  replaced 
by  zinc  dust  or  iron  powder,  but  the  yields  are  usually 
not  so  good. 

i  B.  22,  587.  2  B.  40,  858.  3  B.  35,  162. 

4  B.  34,  3802  ;   38,  725.  5  B.  23,  1226. 


46        PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  s.s'-DINITRODIPHENYL  (NO2[3J 
C6H,i[i.i/]C6H4[3/]NO2).1  Thirty  grammes  of  m.-m tramline 
are  dissolved  or  suspended  in  45  grm.  of  concentrated  sulphuric 
acid  and  60  c.c.  of  water,  and  diazotised  as  usual  with  15-3  grm. 
of  sodium  nitrite.  The  diazo-solution  thus  obtained  is  run 
slowly  and  with  continual  stirring  into  a  cold  solution  of  22  grm. 
of  cuprous  chloride  in  100  c.c.  of  concentrated  hydrochloric 
acid.  When  the  solution  has  become  green  the  reaction 
product  is  filtered  off  and  distilled  in  steam.  m.-Chlornitro- 
benzene  (6  grm.)  passes  over  and  dinitrodiphenyl  remains  in 
the  flask,  and  it  is  collected  and  recrystallised  from  glacial 
acetic  acid.  Yellow  needles.  M.P.  200°.  The  yield  is  87  per 
cent. 

PREPARATION  OF  DIPHENYL  (C6H5.C6H5).2  Thirty-one 
grammes  of  aniline  are  dissolved  in  150  c.c.  of  water  and 
40  grm.  of  concentrated  sulphuric  acid,  and  diazotised  in 
the  usual  way  with  23  grm.  of  sodium  nitrite.  One  hun- 
dred grammes  of  90  per  cent,  alcohol  are  added  and  then 
slowly  50  grm.  of  copper  powder.  The  temperature  of  the 
solution  rises  to  30°— 40°  and  nitrogen  is  evolved.  After 
stirring  for  an  hour  the  whole  is  distilled  in  steam  and  the 
distillate  collected  whenever  a  sample  gives  solid  matter  on 
dilution  with  water.  M.P.  71°.  The  yield  is  about  25  per 
cent. 

FROM  THE  CARBOXYLIC  ACIDS.  The  carboxyl 
group  is  not  easily  reduced,  but  may  be  eliminated  by 
distilling  the  sodium  salt  of  the  acid  with  soda-lime. 
Thus  sodium  benzoate  distilled  with  soda-lime  gives 
benzene  in  good  yield.  The  sulphonic  group  is  often 
similarly  eliminated.  Hydrocarbons  are  also  often 
obtained  by  the  electrolysis  of  the  sodium  salts  of  the 
acids.  Thus  potassium  acetate  on  electrolysis  gives 
ethane  : 

2CH3COOK  +  2H2O  =  CH3 .  CH8+ 2CO2+  2KOH  +  H2, 
and  potassium  succinate  gives  ethylene  : 

CH2.COOK  CH2 

I  +  2H20  =  ||      +  2C02  +  2KOH  +  H2. 

CH2.COOK  CH2 

i   B,  38;  726.  2  B.  23,  1226. 


THE  HYDROCARBONS 


47 


These  methods,  however,  are  of  theoretical  rather 
than  practical  importance. 

FROM  THE  LOWER  HYDROCARBONS  BY 
OXIDATION.  This  reaction  is,  as  a  rule,  of  no  great 
importance  as  a  preparative  method,  but  is  worthy  of 
mention.  The  reaction  only  takes  place  in  the  ali- 
phatic series  in  a  few  cases,  and  then  only  to  a  very 
minor  extent  (yields  i  to  2  per  cent.).  Unsaturated 
compounds,  however,  react  more  readily  than  satu- 
rated ones.  Thus  the  copper  acetylides  are  oxidised 
by  shaking  their  alkaline  solutions  with  air  or  on 
treating  them  with  potassium  ferricyanide.  The 
best-known  case  of  this  reaction  is  the  oxidation  of 
the  copper  salt  of  o.-nitrophenylacetylene  to  the 
corresponding  di-acetylene : 


—NO, 


NO, 


=C— C=C— 
— NO2        NO2— 


and  this  is  one  of  the  steps  in  an  earlier  indigo  synthesis. 
In  the  aromatic  series  the  reaction  takes  place  with 
greater  ease  and  is  usually  carried  out  by  heating 
the  hydrocarbon  with  an  aqueous  solution  of  potassium 
persulphate. 

PREPARATION  OF  DIBENZYL  (C6H5.CH2.CH2.C6H5).i 
Thirty  grammes  of  toluene  are  heated  with  continual  stirring 
for  four  hours  on  the  water-bath  with  a  solution  of  44  grm. 
of  potassium  persulphate  in  500  c.c.  of  water.  The  oily 


32,  432,  2531. 


48        PREPARATION  OF  ORGANIC  COMPOUNDS 

layer  is  then  collected,  dried  with  calcium  chloride,  and 
fractionated.  Toluene  and  benzaldehyde  pass  over  first,  and 
then  between  270°  and  280°  a  mixture  of  benzoic  acid  and 
dibenzyl.  This  portion  of  the  distillate  is  dissolved  in  ether, 
washed  with  dilute  caustic  soda  (to  remove  benzoic  acid), 
the  ether  removed,  and  the  residue  recrystallised  from  dilute 
alcohol.  Yield  about  15  per  cent. 


CHAPTER  III 
HALOGEN  COMPOUNDS 

THE  chief  methods  of  preparing  halogen  compounds 
are  : 

(i)  Replacement  of  hydrogen  by  means  of  (a)  mole- 
cular halogen,  (b)  nascent  halogen,  (c)  halogen 
compounds. 

(ii)  Addition  of  halogen  or  halogen  acid  to  unsatu- 
rated  compounds. 

(iii)  Replacement  of  hydroxyl  by  halogen. 

(iv)  Replacement  of  the  diazo-group  by  halogen. 

(i)  (a)  REPLACEMENT  OF  HYDROGEN  BY 
MEANS  OF  MOLECULAR  HALOGEN.  Chlorine 
reacts  with  methane  in  direct  sunlight  with  explosive 
violence,  carbon  being  deposited  and  hydrochloric 
acid  formed.  In  diffused  daylight  the  hydrogen 
atoms  are  successively  replaced,  carbon  tetrachloride 
being  the  final  product.  As  a  rule,  however,  chlorine 
and  bromine  only  replace  hydrogen  slowly.  With 
iodine  the  reaction  is  usually  too  sluggish  to  be  of  any 
great  practical  importance.  The  reaction  can  be 
greatly  accelerated  by  adding  a  halogen  "  carrier." 
The  most  frequently  used  carriers  are,  iron  and  anhy- 
drous iron  halides,  aluminium  halides,  sulphur,  iodine, 
chlorides  of  antimony,  and  phosphorus  pentachloride. 
Of  these,  iodine,  phosphorus  pentachloride,  and  the 
chlorides  of  antimony  all  direct  the  halogen  to  the  side 
chain  when  employed  in  halogenating  aromatic  com- 
pounds. Heat  and  direct  sunlight  also  have  a  beneficial 
effect  on  the  course  of  the  reaction. 

49  4 


50   PREPARATION  OF  ORGANIC  COMPOUNDS 

It  is  often  necessary  to  dissolve  the  substance  which 
is  to  be  halogenated,  and  the  best  solvents  are  water, 
sulphuric  acid,  chloroform,  carbon  tetrachloride,  and 
glacial  acetic  acid.  In  the  case  of  bromine,  aqueous 
potassium  bromide  is  sometimes  a  convenient  sol- 
vent, as  bromine  is  more  soluble  in  this  than  in 
water. 

As  a  source  of  chlorine  either  a  cylinder  of  the  com- 
pressed gas  can  be  used  or  the  gas  can  be  generated 
by  allowing  concentrated  hydrochloric  acid  to  drop  on 
solid  potassium,  or  better,  calcium  permanganate.  No 
heating  is  required  at  first,  but  when  the  stream  of 
gas  begins  to  slacken  the  flask  should  be  warmed. 
Chlorine  is  best  dried  by  passing  it  through  concen- 
trated sulphuric  acid.  All  corks,  rubber  or  otherwise, 
when  exposed  to  the  action  of  chlorine  or  bromine 
should  be  protected  by  coating  with  paraffin  wax  or 
collodion. 

PREPARATION    OF  MONOCHLORACETIC   ACID 

(CH2C1COOH).  One  hundred  grammes  of  glacial  acetic  acid 
and  10  grm.  of  sulphur  are  placed  in  a  tubulated  glass  retort 
and  the  whole  weighed.  The  retort  is  then  supported  on  a 
sand-bath  with  the  neck  sloping  upwards.  A  condenser  is 
attached  to  the  neck  so  as  to  form  a  sloping  reflux  and 
is  provided  with  a  calcium  chloride  tube.  A  fairly  rapid 
stream  of  dry  chlorine  is  led  in  by  a  tube  passing  through 
the  tubulus  and  reaching  almost  to  the  bottom  of  the  retort. 
The  acid  is  kept  gently  boiling  and  the  stream  of  chlorine 
continued  until  an  increase  in  weight  of  about  38  grm.  has 
taken  place.  This  usually  takes  about  10  hours  but  the 
reaction  is  greatly  facilitated  by  direct  sunlight.  The  liquid 
is  then  poured  off  from  the  sulphur  and  distilled.  The  first 
portions  consist  of  acetyl  chloride,  acetic  acid,  &c.,  and  are 
rejected.  The  fraction  boiling  at  about  i6o°-i9O°  is  collected 
and,  after  cooling,  any  liquid  portion  poured  off  and  the  solid 
then  redistilled.  Colourless  sharp-smelling  crystals.  M.P. 
63°,  B.P.  i85°-i87°.  Yield  about  70  to  80  grm. 

In  halogenating  fatty  acids  the  halogen  always 
attaches  itself  to  the  a-carbon  atom.  The  reaction 
possibly  takes  place  in  the  following  stages  : 


HALOGEN  COMPOUNDS 


CH,.COOH 


/OH 

CH2  :  C< 

XOH 
Enolic  form. 


^-  O;H|  - 
XOH  ' 


->    CH2C1.G(          +HC1 
X3H 

When  halogens  act  on  aromatic  compounds  at  the 
ordinary  temperature  it  is 
the  hydrogen  of  the  nucleus 
that  is  attacked,  whereas 
at  elevated  temperatures 
the  halogen  enters  the  side 
chain.  According  to  Brunei 
and  Vorbrodt,1  when  bro- 
minating  aromatic  com- 
pounds in  solution,  the 
greater  the  ionising  power 
of  the  solvent  the  more 
readily  the  halogen  enters 
the  nucleus. 


PREPARATION  OF  BROMO- 

BENZENE  (C6H5Br).2  Fifty 
grammes  of  benzene  containing 
about  J  grm.  of  pyridine  (to 
act  as  a  halogen  carrier)  are 
placed  in  a  flask  fitted  with 
an  upright  condenser  and  trap 
as  shown  in  Fig.  47.  One 
hundred  and  twenty  grammes 
of  bromine  (40  c.c.)  are  then 
added  and  the  whole  heated 
gently  on  a  water-bath  to  25°- 
30°.  At  this  temperature  a  FIG.  47. 

vigorous  reaction  sets  in  with 

evolution  of  hydrobromic  acid.  When  the  reaction  has 
moderated,  the  temperature  is  slowly  raised  to  65°~7O° 
and  maintained  at  this  point  until  the  evolution  of  hydro- 
bromic acid  has  almost  ceased.  After  cooling,  the  contents 


1  Ch.  Z.  33,  557. 


2  Soc.  76,  894- 


52        PREPARATION  OF  ORGANIC  COMPOUNDS 

of  the  flask  are  well  washed  with  dilute  caustic  soda  (the 
washings  must  react  alkaline),  dried  over  calcium  chloride, 
and  then  distilled.  Unchanged  benzene  passes  over  at  about 
8o°-ioo°  and  is  rejected.  The  higher  boiling  portions  are 
collected  and  fractionated.  Heavy  colourless  oil.  B.P.  155°. 
Yield  60  grm. 

PREPARATION  OF  BENZYL  CHLORIDE  (C^CH^Cl).1 
One  hundred  grammes  of  toluene  and  5  grm.  of  phosphorus 
pentachloride  (to  act  as  chlorine  carrier)  are  placed  in  a  tubu- 
lated retort  connected  with  a  reflux  condenser  carrying  a 
calcium  chloride  tube  at  the  end  (Fig.  8).  The  toluene  is 
boiled  and  a  stream  of  dry  chlorine  is  led  into  the  boiling 
liquid  through  the  tubulus.  This  treatment  is  continued  until 
37  grm.  of  the  gas  have  been  taken  up.  The  liquid  is  then 
fractionated  and  the  fraction  boiling  between  165°  and  185° 
collected  and  repeatedly  refractionated  (best  with  a  column 
apparatus,  see  p.  26),  until  a  fraction  is  obtained  boiling 
at  176°-!  80°.  Colourless  liquid  with  an  irritating  smell. 
B.P.  176°.  Yield  80  to  90  grm. 

The  portions  boiling  above  185°  consist  chiefly  of  benzal 
chloride,  C6H5CHC12,  and  benzotrichloride  (phenylchloroform), 
C6H5CC13. 

PREPARATION  OF  BENZOYL  CHLORIDE  (C6H6COC1).2 
Dry  chlorine  is  led  into  100  grm.  of  cold  benzaldehyde  in  the 
apparatus  described  in  the  previous  preparation.  The  gas  is 
readily  absorbed  with  evolution  of  heat,  and  torrents  of 
hydrochloric  acid  are  given  off.  When  the  reaction  has 
moderated  heat  is  applied  so  as  to  keep  the  liquid  boiling 
briskly,  and  the  stream  of  chlorine  is  continued  until  no  more 
hydrochloric  acid  is  evolved.  A  stream  of  dry  air  or  carbon 
dioxide  is  then  passed  through  the  apparatus  in  order  to 
drive  out  excess  of  chlorine.  Finally  the  product  is  distilled. 
Colourless  fuming  liquid  with  a  very  irritating  smell.  Yield 
almost  quantitative.  This  is  the  technical  method  of  pre- 
paring benzoyl  chloride,  and  thus  obtained  it  always  contains 
rather  more  chlorine  than  required  by  theory.  This  is  due  to 
some  slight  substitution  having  taken  place  in  the  nucleus. 

Hydroxyl- or  amino- groups  attached  to  the  nucleus 
greatly  facilitate  the  entrance  of  halogen.  The 

B.  18,  606;  A.  272,  149.  2  A.  3,  1262. 


HALOGEN  COMPOUNDS  53 

halogen  first  enters  the  para-  and  then  the  two  ortho- 
positions. 

PREPARATION  OF  TRIBROMOPHENOL.  Ten  grammes 
of  phenol  are  dissolved  in  200  c.c.  of  cold  water,  and  52  grm. 
of  bromine  in  aqueous  solution  added.  The  precipitated  tri- 
bromophenol  is  collected,  washed  with  water,  and  recrystallised 
from  dilute  alcohol.  Long  slender  needles  melting  at  95°. 
Yield  quantitative. 

Other  phenols  behave  in  the  same  way  and  the 
reaction  has  been  applied  to  their  quantitative 
estimation.1 

In  brominating  or  chlorinating  primary  amines  it  is 
usually  necessary  to  protect  the  amino-group  from 
the  oxidising  action  of  the  halogen  by  replacing  one 
of  the  hydrogen  atoms.  This  is  best  done  by  forming 
an  acety /-derivative  (see  p.  228). 

PREPARATION    OF    5-BROM  ACET-o.-TOLUIDE.2 

Twenty  grammes  of  acet-o.-toluide  are  dissolved  in  130  grm. 
of  glacial  acetic  acid,  and  bromine-laden  air  is  drawn  through 
the  solution  by  means  of  a  filter- pump  until  the  whole  solidifies 
to  a  white,  crystalline  mass.  The  acetic  acid  is  then  removed 
as  completely  as  possible  by  draining  on  a  Buchner  funnel  at 
the  pump,  and  the  bromacet-o.-toluide  recrystallised  from 
alcohol.  Yield  15  grm.  M.P.  I56°-I57°.  The  acetyl  group 
can  be  removed  by  boiling  with  hydrochloric  acid. 

The  acetic  acid  mother-liquors  from  the  above  preparation 
contain  5-brom-0.-toluidine,  which  has  been  formed  by  the 
saponification  of  the  bromacettoluide  by  the  hydrobromic 
acid  liberated  during  the  reaction.  The  hydro  bromide  of 
the  base  crystallises  out  in  pearly  leaflets  when  the  acetic 
acid  is  removed  by  distillation.  The  free  base  can  be  obtained 
by  steam-distilling  this  from  slightly  alkaline  solution. 
M.P.  58°. 

Secondary  and  tertiary  amines  can  usually  be  directly 
halogenated. 

1  Hans     Meyer,    "Analyse     u.     Konstitutionsermittlung, " 
2nd  ed.  (1909),  p.  467. 

2  B.  25,  868. 


54        PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION       OF      TETRABROMDIPHENYLAMINE. 

Eight  grammes  of  diphenylamine  are  dissolved  in  alcohol  and 
65  grm.  of  bromine  dissolved  in  100  c.c.  of  the  same  solvent 
slowly  added  with  continual  stirring.  The  whole  is  then  poured 
into  about  500  c.c.  of  water,  filtered,  well  washed,  and  recrystal- 
lised  from  alcohol.  Colourless  needles.  M.P.  182°.  Yield 
quantitative. 

(i)  (b)  REPLACEMENT  OF  HYDROGEN  BY 
MEANS  OF  NASCENT  HALOGEN.  Substitution 
often  takes  place  more  readily  when  molecular  halogen 
is  replaced  by  the  nascent  element,  and  in  addition 
the  method  has  the  advantage  of  allowing  the  amount 
of  halogen  used  to  be  more  accurately  regulated. 
The  nascent  halogen  can  be  generated  by  the  action 
of  an  oxidising  agent  (K2Cr2O7,  or,  better,  HHlgO3, 
where  Hlg  stands  for  chlorine,  bromine,  or  iodine) 
on  the  halogen  acid  or  one  of  its  salts  in  the  presence 
of  sulphuric  acid,  e.g.  : 

5NaBr  +  NaBr03  +  3H2SO4  = 
3Na2S04  +  6Br  +  3H2O, 

or  by  the  action  of  halogen  acid  on  a  salt  of  the  type 
HHlgO,  or  the  halogen  can  be  liberated  electrolytically. 
In  the  case  of  bromine  the  element  is  sometimes 
liberated  simply  by  the  action  of  sulphuric  acid  on 
potassium  bromide  : 

2KBr  +  2H2SO4  =  K2S04  +  2H2O  +  SO2  +  2Br. 

The  mixture  of  bromide  and  bromate,  &c.,  can  either 
be  prepared  by  weighing  out  the  individual  salts  or 
excess  of  halogen  is  added  to  aqueous  caustic  soda 
and  the  solution  evaporated  to  dryness  : 


6KOH  +  3Br2  =  sKBr  +  KBr03  +  3H2O. 

The  residue  is  then  dissolved  in  water  and  the 
active  halogen  estimated  by  titration  in  the  ordinary 
way.  It  is  convenient  to  prepare  a  solution  of  such  a 
strength  that  on  acidifying  i  c.c.  liberates  o-i  grm.  of 
halogen. 


HALOGEN  COMPOUNDS  55 

Bromination  and  iodination  of  aromatic  compounds 
can  often  be  conveniently  brought  about  by  means 
of  the  corresponding  sulphur  halides  in  the  presence 
of  nitric  acid  (see  p.  57). 

PREPARATION    OF    2-6  -  DICHLOR  -  4  -  NITRANILINE.1 

Twenty-eight  grammes  of  /?.-nitraniline  are  dissolved  in 
250  c.c.  of  concentrated  hydrochloric  acid  at  50°.  To  this  is 
gradually  added  a  solution  of  16-4  grm.  of  potassium  chlorate  in 
350  c.c.  of  water  at  about  25°.  When  the  whole  of  the  chlorate 
has  been  added  the  solution  is  diluted  with  a  large  volume 
of  water,  and  the  resulting  precipitate  removed  by  nitration 
and  well  washed.  It  may  be  further  purified  by  crystallisa- 
tion from  glacial  acetic  acid  or  a  mixture  of  this  solvent  and 
alcohol.  Yield  87  per  cent.  Lemon-yellow  needles.  M.P. 
i85°-i88°. 

PREPARATION  OF  a-BROMNAPHTHALENE.  Seventy 
grammes  of  bromine  are  dissolved  in  350  c.c.  of  10  per  cent. 
caustic  soda.  Twenty-five  grammes  of  finely  powdered 
naphthalene,  and  then  with  continual  stirring  250  c.c.  of  10  per 
cent,  hydrochloric  acid,  are  added  slowly  through  a  tube 
reaching  to  the  bottom  of  the  vessel.  Oily  a-bromnaphthalene 
forms  and  is  collected  and  washed,  first  with  10  per  cent. 
sodium  carbonate  solution  and  then  with  water.  The  oil  is 
then  heated  to  200°  until  no  more  hydrobromic  acid  (present  as 
an  addition  compound)  is  evolved.  It  is  finally  distilled,  and 
the  distillate  passing  over  between  200°  and  210°  collected. 
Colourless  liquid.  B.P.  208°. 

PREPARATION    OF     2.6-DIBROMSULPHANILIC     ACID. 

Seventeen  grammes  of  sulphanilic  acid  are  dissolved  in  500  c.c. 
of  hot  water,  and  to  the  solution  thus  obtained  a  solution  of 
10  grm.  of  bromine  in  125  c.c.  of  13  per  cent,  caustic  soda  is 
added.  By  means  of  a  tube  reaching  to  the  bottom  of  the 
vessel  21  grm.  of  concentrated  hydrochloric  acid  are  then 
slowly  run  in  with  continual  stirring.  When  all  the  acid 
has  been  added,  the  solution  is  carefully  neutralised  with 
caustic  soda  and  a  concentrated  solution  of  25  grm.  of  crystal- 
lised barium  chloride  added.  The  precipitated  barium  salt, 
which  contains  two  molecules  of  water  of  crystallisation,  is 

*  B.  36,  43Qi. 


56        PREPARATION  OF  ORGANIC  COMPOUNDS 

collected  by  filtration  after  the  solution  has  cooled.  To  obtain 
the  free  acid  the  barium  salt  is  suspended  in  water  and  decom- 
posed with  the  calculated  amount  of  sulphuric  acid.  The 
precipitated  barium  sulphate  is  removed  by  filtration  and  the 
clear  filtrate  concentrated  until  crystallisation  sets  in.  On 
cooling,  2.6-dibromsulphanilic  acid  separates  out  in  long 
needles  containing  two  molecules  of  water.  It  is  easily  soluble 
in  cold  water  and  hot  alcohol.  When  heated  it  decomposes 
at  about  180°. 

(i)  (c)  REPLACEMENT  OF  HYDROGEN  BY 
MEANS  OF  HALOGEN  COMPOUNDS.  Hydrogen 
is  often  conveniently  replaced  by  halogen  by  means  of 
halogen  compounds.  The  most  frequently  employed 
of  these  latter  are  the  halides  of  phosphorus  and 
sulphur,  antimony  pentachloride,  sulphuryl  chloride, 
and  iodine  chloride.  Further,  in  the  case  of 
quinonoid  compounds,  prolonged  heating  with  halogen 
acid  sometimes  causes  the  entrance  of  halogen  into  the 
ring,  but  this  method  is  only  of  theoretical  interest. 
Bleaching  powder  has  also  been  employed  as  a 
chlorinating  agent,  the  most  notable  case  being  in 
the  preparation  of  chloroform  (see  p.  78). 

PHOSPHORUS  HALIDES.  The  halogen  first  enters  the 
side-chain  and  does  not  enter  the  nucleus  until  the 
hydrogen  of  all  the  side-chains  is  completely  replaced. 
Thus  o-  and  ^>-xylene,  when  heated  with  PC15  under 
pressure  at  200°,  give  CCl3C6H4CHCl2and  (CC13)2C6H4.1 
For  chlorinating,  however,  the  method  is  of  but  minor 
importance,  but  is  sometimes  of  great  use  in  bromi- 
nating.  In  this  case  it  is  usual  not  to  employ  separately 
prepared  phosphorus  bromide,  but  rather  a  mixture 
of  bromine  and  red  phosphorus,  and  care  must  be  taken 
to  use  a  good  sample  of  the  latter,  as  red  phosphorus 
often  contains  considerable  quantities  of  the  yellow 
variety,  and  this  reacts  with  bromine  with  extreme 
violence.  Also  it  is  usually  necessary  to  have  the 
reagents  perfectly  dry,  and  as  red  phosphorus  nearly 
always  contains  phosphoric  acid,  it  must  be  well 

1  C.  r.  102,  689. 


HALOGEN  COMPOUNDS  57 

washed  with  water  until  the  wash-liquors  are  no  longer 
acid  in  reaction,  and  then  carefully  dried.  The  bro- 
mine must  be  dried  by  shaking  with  concentrated 
sulphuric  acid. 

PREPARATION  OF  MONOBROMSUCCINIC  ACID. 
CH2.COOH(i) 

This  preparation  is  best  carried  out  in  a 
CHBr.COOH. 

tubulated  retort  the  neck  of  which  is  sealed  into  a  Liebig's 
condenser.  The  end  of  the  condenser  should  be  connected 
with  an  absorption  apparatus  as  shown  in  Fig.  47  (p.  51), 
in  order  to  prevent  the  escape  of  the  hydrobromic  acid  and 
bromine  fumes  into  the  air.  An  intimate  mixture  of  18  grm. 
of  carefully  dried  succinic  acid  and  3-5  grm.  of  red  phosphorus 
is  placed  in  the  retort  and  80  grm.  of  bromine  are  added  slowly 
by  means  of  a  dropping  funnel  through  the  tubulus.  At  first 
each  drop  of  bromine  causes  a  very  violent  reaction,  and  there- 
fore care  must  be  taken  not  to  add  more  than  a  drop  at  a  time. 
When  all  the  bromine  has  been  added  the  whole  is  heated  on 
the  water-bath  until  the  bromine  has  disappeared.  The  retort 
now  contains  monobromsuccinyl  bromide  formed  according 
to  the  equation  : 

CH2.COOH 
3   |  +  2P  +  8Br2  = 

CH2.COOH 

CHBr.COBr 

3   |  +  2HP03  +  7HBr. 

CH2.COBr 

In  order  to  decompose  this  and  obtain  the  acid,  the  contents 
of  the  retort  are  poured  slowly  into  100  c.c.  of  boiUng 
water  contained  in  a  basin  from  which  the  flame  has  been 
withdrawn.  When  all  the  bromide  has  been  added,  the 
whole  is  filtered,  cooled,  and  repeatedly  extracted  with  ether. 
The  united  ethereal  extracts  are  distilled  on  the  water-bath, 
and  the  solid  residue  of  monobromsuccinic  acid  recrystallised 
from  a  little  water.  It  melts  at  160°.  The  yield  is  80  to  90  per 
cent. 

SULPHUR  HALIDES.  The  chlorides  of  sulphur  have 
met  with  no  success  as  chlorinating  agents,  but  excel- 

i  A.  242, 145;  6.14,892. 


58   PREPARATION  OF  ORGANIC  COMPOUNDS 

lent  results  are  often  obtained  by  using  the  bromide 
or  iodide  in  the  presence  of  nitric  acid.  The  halogen 
exclusively  enters  the  nucleus  and  only  monobrom- 
or  monoiodo-compounds  are  obtained.1  The  reaction 
is  carried  out  as  follows.  The  hydrocarbon  to  be 
halogenated  is  dissolved  in  about  4  parts  of  ligroin, 
and  the  solution  thus  obtained  poured  on  to  about 
3  parts  of  nitric  acid  (D  —  1-4).  Excess  of  sulphur 
bromide  is  then  slowly  added  with  careful  cooling 
during  about  three  hours.  The  upper  layer  is  then 
separated,  washed  first  with  dilute  caustic  potash 
and  then  with  water,  the  ligroin  distilled  off,  and  the 
brominated  compound  distilled  with  steam  and  then 
fractionated.  When  preparing  iodine  compounds  by 
this  method  it  is  usually  necessary  to  heat  the  reaction 
mixture,  and  a  more  dilute  acid  (D  —  1-34)  is  employed. 
The  yields  are  usually  from  80  to  95  'per  cent,  of  theory. 
In  some  cases  nitration  takes  place  simultaneously  to 
a  small  extent. 

PREPARATION  OFa-BROMNAPHTHALENE.  Fifty 
grammes  of  naphthalene  are  dissolved  in  200  c.c.  ligroin  and  the 
solution  poured  on  to  200  c.c.  of  nitric  acid  (D  =  1-4).  The 
vessel  is  then  surrounded  with  a  freezing  mixture  of  ice  and 
salt,  and  when  the  temperature  has  fallen  to  o°,  120  grm.  of 
sulphur  bromide  are  slowly  added  during  about  three  hours. 
The  ligroin  layer  is  then  separated,  washed  with  dilute  caustic 
soda  and  then  with  water.  The  ligroin  is  distilled  off,  and  the 
residue,  which  contains  about  5  per  cent,  of  nitronaphthalene, 
reduced  with  tin  and  hydrochloric  acid  (10  grm.  of  tin  and  about 
200  c.c.  of  20  per  cent,  acid),  and  then  steam-distilled.  The 
naphthylamine  remains  behind  as  the  hydrochloride,  whereas 
the  bromonaphthalene  passes  over.  It  is  separated  from  the 
water  and  redistilled  over  a  little  solid  potash.  It  forms  a 
colourless  oil  boiling  at  280°. 

PREPARATION  OF  4-IODO-W.-XYLENE.  Ten  grammes 
of  w.-xylene  are  dissolved  in  80  c.c.  of  ligroin,  and  the  solution 
thus  obtained  poured  on  to  120  c.c.  of  nitric  acid  (D  =  1-34). 

1  Durol  gives  a  dibro  mo -compound. 


HALOGEN  COMPOUNDS  59 

Twenty  grammes  of  powdered  sulphur  iodide  are  then  added 
and  the  whole  heated  on  the  water-bath  under  a  reflux  con- 
denser for  three  to  four  hours.  The  ligroin  layer  is  then 
separated,  washed  with  dilute  caustic  soda,  and  the  ligroin 
distilled  off.  The  residue  is  steam-distilled,  and  the  oil  which 
comes  over  collected  and  distilled  over  a  little  solid  potash. 
Colourless  oil  boiling  at  220°.  Yield  75  per  cent. 

ANTIMONY  PENTACHLORIDE.  Antimony  penta- 
chloride  is  sometimes  useful  for  chlorinating  and  is 
converted  in  the  process  into  the  trichloride.  It  is 
occasionally  used  in  the  presence  of  iodine  for  the 
exhaustive  chlorination  of  aliphatic  compounds  of 
high  molecular  weight,  such  as  palmitic  acid.1  It  is 
also  capable  of  chlorinating  aromatic  compounds  in 
the  nucleus. 

PREPARATION   OF   3-4-DICHLORBENZOIC  ACID.2    Ten 

grammes  of  ^.-chlorbenzoic  acid  and  75  grm.  antimony 
pentachloride  are  heated  in  a  sealed  tube  to  200°  for  about 
eight  hours.  After  cooling,  the  tube  is  opened  and  the  contents 
treated  with  excess  of  dilute  hydrochloric  acid.  The  preci- 
pitated acid  is  collected,  washed  with  cold  water,  and  dissolved 
in  dilute  ammonia.  After  filtration  the  solution  is  evaporated 
to  dryness  and  the  ammonium  salt  decomposed  with  dilute 
hydrochloric  acid.  The  acid  is  collected,  washed,  and  dried 
in  the  usual  way.  It  is  recrystallised  from  dilute  alcohol 
and  forms  colourless  crystals  melting  at  2Oi°-2O2°. 

SULPHURYL  CHLORIDE  (SO2C12).  Sulphuryl  chloride 
is  useful  for  replacing  hydrogen  atoms  when  in  the 
a-position  to  carbonyl  or  carboxyl  groups.  In  some 
cases  oxidation  takes  place  simultaneously.  Thus 
when  hydroquinone  in  ethereal  solution  at  o°  C.  is 
treated  with  sulphuryl  chloride,  first  y-dichlorquinone 
and  finally  chloranil  is  formed.3 

1  B.  16,  2870  ;    24,  1025. 

2  A.  179,  283. 

3  G.  24,  [2]  375  ;  B.  28  ;  R.  72. 


6o        PREPARATION  OF  ORGANIC  COMPOUNDS 
OH  O  O 


Cl  Cl/   XiCl 


Cl  CL       JC1 


OH  O  O 

It  has  also  been  used  for  chlorinating  various 
aromatic  compounds  both  in  the  side-chain  and  in  the 
nucleus.1 

PREPARATION    OF    MONOCHLORMALONIC   ACID, 

CHC1(COOH)2.2  Carefully  dried  malonic  acid  (10-4  grm.)  is 
dissolved  in  300  c.c.  of  absolute  ether  (dried  over  sodium), 
and  1 3 '5  grm.  of  sulphuryl  chloride  slowly  added  with  careful 
cooling.  When  the  reaction  is  over,  the  ether  is  removed  by 
distillation  and  the  residue  set  aside  in  a  vacuum  desiccator 
over  concentrated  sulphuric  acid  until  crystallisation  takes 
place.  Colourless  crystals.  M.P.  133°.  Yield  almost  quan- 
titative. * 

In  the  same  way,  by  using  twice  the  quantity  of  sulphuryl 
chloride,  dichlormalonic  acid  can  be  obtained.  In  this  case 
it  is  best,  after  removing  the  ether,  to  dissolve  the  residue  in 
alcohol,  pass  in  dry  hydrochloric  acid  gas,  and  then  fractionate 
the  ester  thus  formed. 

For  the  preparation  of  monochloracetic  acid  by 
heating  acetic  acid  with  sulphuryl  chloride  under 
pressure,  the  reader  is  referred  to  D.R.P.  146,796; 
160,102 ;  and  162,894 ;  or  at  the  ordinary  pressure  in 
presence  of  acetyl  chloride,  D.R.P.  157,816.  The  yields 
are  said  to  be  excellent. 

IODINE  CHLORIDE.  Iodine  monochloride  is  used 
for  replacing  hydrogen  by  iodine.  It  is  usual  to 
work  in  glacial  acetic  or  dilute  hydrochloric  acid 
solution. 

1  Z.  Ch.  1866,  705  ;  B.  26,  2942  ;  £).R.P.  139,552  ;  158,951  ; 
160,102  ;  162,394. 

2  B.  35,  1814. 


HALOGEN  COMPOUNDS  61 

PREPARATION  OF  IODONITR ANILINE  (2.4.1).!  Ten 
grammes  of  /?-nitraniline  are  dissolved  in  the  least  possible 
quantity  of  cold  glacial  acetic  acid,  and,  with  continual 
stirring,  a  solution  of  17-8  grm.  of  iodine  chlorine  in  the  same 
solvent  added  slowly.  When  all  the  iodine  chloride  has  been 
added  the  whole  is  allowed  to  stand  for  one  hour  and  then 
poured  into  1000  c.c.  of  boiling  water.  After  boiling  for 
a  few  minutes  the  solution  is  filtered,  and  on  cooling,  the  filtrate 
deposits  long  yellow  needles  of  2-iodo-4-nitraniline,  melting 
at  105°.  By  working  at  a  higher  temperature  and  using 
double  the  quantity  of  iodine  chloride,  2.6-di-iodo-4-nitraniline 
is  obtained. 

BLEACHING  POWDER.  Bleaching  powder  has  met 
with  very  extensive  use  in  the  preparation  of  chloro- 
form (see  p.  78),  and  has  also  been  used  as  a  chlorinat- 
ing agent  where  simultaneous  oxidation  is  not  desired. 

PREPARATION  OF  ACET-£.-CHLORANILIDE.2  Five 
grammes  of  acetanilide  are  dissolved  with  gentle  warming 
in  a  mixture  of  10  grm.  of  glacial  acetic  acid  and  10  grm.  of 
alcohol.  The  solution  is  then  diluted  with  100  c.c.  of  water 
and  heated  to  50°.  At  this  temperature  100  c.c.  of  a  cold,  10 
per  cent,  solution  of  bleaching  powder  are  slowly  added  with 
continual  stirring.  The  acet-£.-chloranilide  is  collected,  washed 
with  water,  and  recrystallised  from  alcohol  or  dilute  acetic 
acid.  Colourless  needles.  M.P.  172-5°. 

(ii)  ADDITION  OF  HALOGEN  OR  HALOGEN 
ACID 

(a)  ADDITION  OF  HALOGEN.  Chlorine  and  bro- 
mine are,  as  a  rule,  readily  taken  up  by  compounds  con- 
taining a  double  or  triple  bond,  whereas  iodine  but 
rarely  reacts  in  this  way.  Compounds  containing  a 
conjugated  double  bond,  —  C=C  — C=C— ,  react 
abnormally  and  on  the  addition  of  halogen  give  a 


-CHk-C=C-CHlff-. 


substance     of     the     type      — CHlg-C=C~CHlg- 
An   explanation   of   this   behaviour   is   furnished   by 
Thiele's  theory  of  latent  valencies. 

1  B-  34.  3344-  2  A.  182,  98. 


62        PREPARATION  OF  ORGANIC  COMPOUNDS 

When  bringing  about  such  addition-reactions  the 
most  usual  solvents  are  CS2,  CC14,  glacial  acetic  acid,  and 
ether.  When  forming  addition  compounds  with  the  ter- 
penes,  Wallach  recommends  alcohol  as  a  solvent.  As 
a  rule  better  results  are  obtained  with  bromine  than 
with  chlorine,  as  in  the  latter  case  there  is  more  danger 
of  substitution  taking  place  simultaneously. 

PREPARATION  OF  ETHYLENE  DIBROMIDE.1  A  fairly 
rapid  stream  of  ethylene  is  generated  from  alcohol  and  sul- 
phuric or  phosphoric  acid  {see  p.  40),  and  after  washing,  first 
with  water  and  then  with  dilute  caustic  soda,  is  passed  into 
100  grm.  of  bromine  contained  in  a  vessel  surrounded  by  cold 
water  or  ice.  The  stream  of  gas  is  continued  until  the  bromine 
is  decolorised.  The  oily  liquid  is  then  washed  with  dilute 
caustic  soda  solution,  dried  with  calcium  chloride,  and  finally 
distilled.  Colourless  oily  liquid,  freezing  at  8°  and  boiling  at 
131°. 

PREPARATION  OF  CINNAMIC  ACID  DIBROMIDE 
(Ph .  CHBr .  CHBr .  COOH)  .2  Twenty-five  grammes  of  cinnamic 
acid  are  dissolved  in  100-125  c.c.  of  dry  ether  and  the  whole 
cooled  to  o°  by  surrounding  with  ice  or  a  freezing  mixture. 
Twenty-seven  grammes  of  bromine  are  then  slowly  added,  and, 
as  the  reaction  is  very  violent  in  direct  sunlight,  care  must  be 
taken  to  exclude  all  but  diffused  light.  When  all  the  bromine 
has  been  added,  the  solution,  which  should  be  colourless,  is 
transferred  to  a  distilling  flask  and  the  ether  removed  by 
distillation.  The  residue  is  then  recrystallised  from  dilute 
alcohol.  Instead  of  distilling  off  the  ether,  the  acid  can  be 
extracted  by  shaking  out  with  dilute  caustic  soda  solution, 
and  then  precipitated  from  the  aqueous  extract  by  acidifying 
with  hydrochloric  acid.  Colourless  leaflets.  M.P.  195°.  Yield 
almost  quantitative. 

PREPARATION    OF    CINNAMIC    ACID     DICHLORIDE.3 

This  experiment  must  be  carried  out  in  direct  sunlight.  Fifteen 
grammes  of  finely  powdered  cinnamic  acid  are  suspended  in 
120  grm.  of  freshly  distilled  carbon  bisulphide,  and  the  whole 
saturated  with  dry  chlorine  until  of  a  greenish  yellow  colour. 

1  A.  168,  64  ;   192,  244. 

2  A.  195,  140. 

3  B.  14,  1867. 


HALOGEN  COMPOUNDS  63 

The  solution  is  then  violently  shaken  until  the  colour  has 
disappeared,  resaturated  with  chlorine,  and  this  process 
repeated  until  rather  more  than  the  calculated  weight  of 
chlorine  (6-5  grm.)  has  been  taken  up.  The  precipitated  acid 
is  then  collected  by  nitration  and  recrystallised  from  dilute 
alcohol.  Colourless  leaflets  melting  with  slight  decomposition 
at  i62°-i64°.  Yield  90  to  95  per  cent. 

When  the  addition  of  chlorine  takes  place  in  the  dark  a 
totally  different  but  isomeric  substance  is  formed.  For 
experimental  details,  &c.,  see  B.  27,  2041. 

(b)  ADDITION  OF  HALOGEN  ACID.1  Hydriodic 
acid  adds  on  most  readily,  hydrobromic  acid  less 
readily,  and  hydrochloric  acid,  as  a  rule,  only  with 
difficulty,  but  the  terpenes  often  readily  form  addition 
compounds  with  this  last.  In  unsymmetrical  com- 
pounds, e.g.  CH3.CH  :  CH2,  the  halogen  attaches  itself 
to  the  carbon  atom  which  is  poorest  in  hydrogen  2 
(MarkownikofFs  rule). 

PREPARATION  OF  ft  -  PHENYL  -  ft  -  BROMPROPIONIC 
ACID  (Ph.CHBr.CH2COOH).3  Ten  grammes  of  finely  pow- 
dered cinnamic  acid  are  shaken  for  two  days  with  50  c.c.  of 
an  aqueous  solution  of  hydrobromic  acid  saturated  with  the 
gas  at  o°.  The  precipitate  is  then  collected,  washed  with  a 
little  ice-water,  pressed  between  filter-paper,  and  dried  in  vacua 
over  solid  potash  at  the  ordinary  temperature.  A  more 
expeditious  method  is  to  saturate  glacial  acetic  acid  at  the 
ordinary  temperature  with  hydrobromic  acid  (i  part  of 
glacial  acetic  acid  dissolves  about  0-6  part  of  HBr),  and  then 
to  heat  the  solution  thus  obtained  with  the  cinnamic  acid  in  a 
sealed  tube  at  100°  for  two  hours.  On  cooling,  the  addition 
compound  crystallises  out.  As  bromhydrocinnamic  acid  is 
very  readily  decomposed  by  water  it  can  only  be  recrystallised 
from  anhydrous  media.  For  this  purpose  carefully  dried 
carbon  bisulphide  is  best,  as  bromhydrocinnamic  acid  is  only 
slightly  soluble  in  this  medium  in  the  cold,  whereas  cinnamic 
acid  itself  is  readily  dissolved.  Colourless  crystals.  M.P.  137°. 

1  Methods  of  generating  hydrochloric  and  hydrobromic  acid 
gases  will  be  found  discussed  on  p.  70. 

2  A.  153,  256  ;    145,  274  ;    B.  2,  660. 

3  B.   II,  I22J. 


64        PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION     OF      LIMONENE      HYDROCHLORIDE.* 

For  the  success  of  this  experiment  the  total  exclusion  of  every 
trace  of  moisture  is  absolutely  necessary.  Twenty  grammes  of 
limonene,  which  has  been  dried  over  metallic  sodium,  is  dis- 
solved in  its  own  volume  of  carefully  dried  carbon  bisulphide. 
The  solution  is  placed  in  a  dry  distilling  flask,  the  side-tube  of 
which  is  connected  with  a  calcium  chloride  tube  to  prevent 
the  entrance  of  atmospheric  moisture.  The  flask  is  surrounded 
with  ice,  and  a  stream  of  dry  hydrogen  chloride  gas  led  into  the 
mixture  through  the  neck.  After  the  gas  has  been  passed 
for  about  eight  hours  the  operation  is  interrupted,  the  carbon 
bisulphide  removed  by  distillation  from  the  water-bath,  and 
the  residue  then  fractionated  in  vacuo.  The  monohydro- 
chloride  passes  over  at  97°-98°  (11-12  mm.).  It  forms  a 
colourless  liquid  : 

CHa      Cl 


(iii)  REPLACEMENT  OF  OXYGEN  OR  HYDROXYL 
BY  HALOGEN 

The  oxygen  in  ketones,  aldehydes,  and  acid  amides, 
and  the  hydroxyl  group  in  alcohols  and  carboxylic 
and  sulphonic  acids,  can  usually  be  replaced  by  halogen 
atoms  by  means  of  a  variety  of  substances.  The  most 
important  of  these  will  now  be  discussed. 

PHOSPHORUS  PENTACHLORIDE.  Phosphorus  penta- 
chloride  replaces  the  oxygen  or  hydroxyl  in  all  types 
of  substances  mentioned  above  : 

2ROH  +  PC15  =  2RC1  +  POC13  +  H20 
R  :  O  +  PC15  =  RC12  +  POC13. 

It  is  used  either  alone  or  in  the  presence  of  a  solvent 
such  as  acetyl  chloride,  chloroform,  phosphorus  oxy- 
chloride,  benzene,  ligroin,  or  ether.     The  phosphorus 
1  A.  270,  1 88. 


HALOGEN  COMPOUNDS  65 

oxychloride  formed  is  usually  removed  by  fractional 
distillation  in  vacuo.  This  reaction  is  the  one  most 
frequently  used  for  preparing  ketone  and  acid  chlorides. 
The  use  of  acetyl  chloride  as  a  solvent  was  introduced 
by  Emil  Fischer,  and  has  proved  especially  useful  for 
preparing  the  chlorides  of  amino-acids.  Phosphorus 
pentabromide  has  met  with  but  little  success  for 
preparing  bromine  compounds. 

PREPARATION  OF  BENZOYL  CHLORIDE  (PhCOCl). 
Fifty  grammes  of  dry  benzole  acid  are  mixed  with  90  grm.  of 
powdered  phosphorus  pentachloride.  The  reaction,  which 
commences  at  the  ordinary  temperature,  is  completed  by  heat- 
ing for  a  short  time  on  the  water-bath.  The  phosphorus 
oxychloride  (B.P.  110°)  and  the  benzoyl  chloride  (B.P.  200°) 
are  then  separated  by  fractional  distillation.  Colourless, 
fuming  oil  with  pungent  odour.  Yield  90  per  cent. 

PREPARATION  OF  HIPPURYL  CHLORIDE  (PhCONH. 
CHaCOCl).1  Ten  grammes  of  dry  hippuric  acid  are  finely 
powdered,  sifted  through  a  very  fine  sieve,  and  then  added  to  a 
solution  of  13  grm.  of  phosphorus  pentachloride  in  100  grm.  of 
acetyl  chloride.  The  whole  is  violently  agitated  on  a  shaking- 
machine  for  two  hours.  The  resulting  crystals  are  collected, 
washed  with  dry  petroleum  ether,  and  dried  in  a  vacuum  desic- 
cator over  concentrated  sulphuric  acid.  If  desired,  they  may 
be  further  purified  by  recrystallisation  from  warm  acetyl 
chloride,  but  prolonged  heating  must  be  avoided,  as  otherwise 
decomposition  will  take  place  and  a  yellow  substance  be  formed. 
At  all  stages  of  the  preparation  moisture  should  be  avoided 
as  far  as  possible.  Colourless  needles.  On  heating,  it  becomes 
yellow  at  about  125°,  then  red,  and  finally  melts  indefinitely  at 
higher  temperatures.  Yield  80  per  cent. 

PREPARATION  OF  NAPHTHALENE  SULPHO- 
CHLORIDES  (C10H7SO2C1).2  Forty  grammes  of  sodium  a-  or 
/3-naphthalene  sulphonate  are  dried  at  150°,  and  while  still 
warm  are  gradually  added  to  an  equal  weight  of  coarsely 
powdered  phosphorus  pentachloride.  The  reaction  takes 
place  without  heating,  and  the  addition  of  the  salt  is  so  regu- 
lated that  it  does  not  become  too  violent.  When  the  whole  has 

i  B.  38,  612.  2  A.  275,  233. 

5 


66        PREPARATION  OF  ORGANIC  COMPOUNDS 

been  added  the  mixture  is  heated  on  the  water-bath  until  it 
has  become  homogeneous,  and  most  of  the  phosphorus  oxy- 
chloride  then  removed  by  distillation  under  slightly  reduced 
pressure  (500  mm.  100°  C.).  When  20-25  grm-  of  the  oxy- 
chloride  have  been  collected,  the  distillation  is  stopped  and  the 
contents  of  the  flask  poured  into  a  basin  and  allowed  to  cool 
with  continual  stirring.  The  crystalline  mass  thus  obtained  is 
ground  up  with  ice-cold  water,  filtered,  and  the  precipitate 
melted  by  careful  heating  on  the  water-bath.  The  water  it 
has  retained  rises  to  the  surface  and  is  removed  as  far  as  pos- 
sible by  absorbing  it  with  filter -paper.  On  cooling,  the  sulpho- 
chloride  sets  to  a  solid  mass.  This  is  powdered  and  dried  in 
vacuo  over  sulphuric  acid.  It  is  then  recrystallised  from  a 
mixture  of  benzene  and  petroleum  ether.  Colourless  crystal- 
line solids.  The  a-chloride  melts  at  66°,  the  /3-chloride  at 
76°.  Yields  60  and  70  per  cent,  respectively. 

PREPARATION     OF     o.-NITROBENZYL     CHLORIDE 

(C6H4[i]NO2[2]CH2Cl).i  Five  grammes  of  o.-nitrobenzyl 
alcohol  are  dissolved  in  50  grm.  of  dry  chloroform,  and  3  grm. 
of  powdered  phosphorus  pentachloride  added  to  the  well- 
cooled  liquid.  When  the  reaction  is  over,  the  whole  is  shaken 
up  with  cold  water,  the  chloroform  layer  collected,  and  the 
chloroform  removed  by  distillation  from  the  water -bath. 
o.-Nitrobenzyl  chloride  is  left  as  a  mass  of  pale  yellow  needles 
which  melt  at  49°.  It  may  be  recrystallised  from  chloroform. 

PREPARATION     OF     BENZOPHENONE     CHLORIDE 

(Ph2CCl2)  .2  Twenty-four  grammes  of  benzophenone  are  mixed 
with  40  grm.  of  phosphorus  pentachloride  and  the  whole 
heated  under  a  reflux  condenser  on  the  oil-bath  to  a  tempera- 
ture of  220°-240°  for  four  hours.  The  resulting  mixture  is 
then  submitted  to  fractional  distillation  in  vacuo,  the  benzo- 
phenone chloride  passing  over  at  193°  at  30  mm.  pressure. 

PHOSPHORUS  OXYCHLORIDE.  Phosphorus  oxy- 
chloride  does  not  attack  ketonic  groups  except  when 
these  are  capable  of  reacting  in  the  enolic  form,  e.g. 
uric  acid.  It  does  not  form  acid  chlorides  from 
carboxylic  acids,  but  only  from  their  sodium  salts. 
It  replaces  alcoholic  hydroxyl  and  can,  therefore,  be 

1  B.  18,  2402.  2  B.  3,  752  ;  29,  2944. 


HALOGEN  COMPOUNDS  67 

used  for  preparing  chloro-acids  from  the  corresponding 
oxy-acids,  the  carboxyl  group  remaining  intact.  It 
leaves  no  volatile  phosphorus  compound  as  it  is  changed 
into  phosphoric  acid,  and  in  cases  where  the  required 
halogen  compound  can  be  distilled  this  considerably 
facilitates  the  separation. 

PREPARATION    OF    DIPHENYL    CHLORACETIC    ACID 

(Ph2CClCOOH)  .1  Twenty  grammes  of  benzylic  acid,  Ph2C(OH> 
COOH,  are  gently  warmed  with  an  equal  weight  of  phos- 
phorus oxychloride  until  the  acid  goes  into  solution  and 
a  red  colour  begins  to  make  its  appearance.  The  whole  is 
then  allowed  to  cool  and  the  crystalline  mass  thus  obtained 
shaken  with  a  litre  of  cold  water  until  the  acid  has  become 
quite  solid  and  hard  (one  to  two  hours).  It  is  then  collected, 
washed  with  water,  dried,  and  recrystallised  from  a  mixture 
of  benzene  and  ligroin.  Colourless  rhombic  tablets.  M.P. 
n8°-ii9°  (decomp.).  Yield  65  per  cent. 

PREPARATION  OF  2.6-DICHLORURIC  ACID.2  Twenty 
grammes  dry  potassium  urate  are  heated  with  24  grm. 
of  phosphorus  oxychloride  for  six  hours  in  a  sealed  tube 
at  a  temperature  of  i6o°-i7O°.  After  cooling,  the  tube  is 
opened  (there  is  considerable  pressure)  and  the  dark-coloured 
mass  poured  into  water,  filtered,  and  the  precipitate  dried 
and  powdered.  It  is  then  added  slowly  to  5  parts  of  nitric 
acid  (D  =  1-4),  and  the  whole  boiled  for  twenty  to  thirty 
minutes.  The  greater  part  of  the  dichloruric  acid  remains 
undissolved  and  the  rest  is  recovered  by  precipitating  with 
water.  The  crude  acid  is  now  well  washed,  suspended  in 
24  parts  of  boiling  alcohol,  and  aqueous  ammonia  added  little 
by  little  until  the  whole  goes  into  solution  with  the  exception 
of  a  few  brown  flocks.  These  are  removed  by  nitration  and 
the  nitrate  boiled  with  animal  charcoal,  and  again  filtered. 
On  sharply  cooling  the  nitrate,  the  ammonium  salt  separates 
out  as  large  pale  yellow  leaflets,  the  yield  being  about  6  grm. 
A  further  quantity  of  the  salt  can  be  obtained  by  concentra- 
ting the  mother-liquors .  To  obtain  the  free  acid  the  ammo- 
nium salt  is  dissolved  in  water  and  then  acidified  with  mineral 
acid.  The  2-6-dichloruric  acid  is  precipitated  and  is  collected 
in  the  usual  way.  It  should  form  a  colourless  crystalline 
powder  which  does  not  melt. 

i  B.  36,  145-  2  B.  30,  2208. 


68        PREPARATION  OF  ORGANIC  COMPOUNDS 

PHOSPHORUS  TRICHLORIDE.  Phosphorus  trichloride 
replaces  alcoholic,  phenolic,  and  carboxylic  hydroxyl 
groups,  and  in  the  preparation  of  the  chlorides  of  the 
lower  fatty  acids  is  usually  to  be  preferred  to  the 
pentachloride.  It  has  the  advantage  of  leaving  no 
volatile  phosphorus  compounds,  and  whereas  one 
molecule  of  the  trichloride  gives  three  molecules  of 
acid  chloride,  one  molecule  of  the  pentachloride  gives 
only  one  molecule  of  the  acid  chloride  : 

3R.COOH  4-  PC13  =  sRCOCl  +  P(OH)3 
R.COOH  +  PC15  =  RCOC1  +  POC13  +  HC1. 

It  is  especially  useful  for  preparing  derivatives  from 
acid  chlorides,  e.g.  acid  amides,  without  isolating  the 
chloride  in  the  pure  state  (see  p.  220).  PHOSPHORUS 
TRIBROMIDE  and  TRI-IODIDE  have  also  been  used  for 
replacing  hydroxyl  groups  by  halogen,  but  the  yields 
are  not  so  good  as  in  the  case  of  the  chlorine  compounds, 
and  it  is  better  to  use  a  mixture  of  the  halogen  and  red 
phosphorus,  in  which  case  substitution  at  the  a-carbon 
atom  also  takes  place  (see  p.  57). 

PREPARATION  OF  ACETYL  CHLORIDE  (CH3COC1). 
One  hundred  grammes  of  glacial  acetic  acid  are  placed  in  a 
distilling  flask  which  is  cooled  by  immersion  in  cold  water. 
Eighty  grammes  of  phosphorus  trichloride  are  then  slowly 
added  with  continual  shaking.  When  the  whole  of  the  tri- 
chloride has  been  added,  the  mixture  is  gently  warmed  until  no 
more  hydrochloric  acid  is  evolved.  It  is  then  distilled  from 
the  water-bath  and  the  distillate  further  purified  by  a  second 
distillation.  The  acetyl  chloride  passes  over  at  55°  as  a  colour- 
less, strongly  fuming  liquid  with  a  pungent  and  irritating 
odour.  It  must  be  carefully  protected  from  atmospheric 
moisture  as  it  is  readily  decomposed.  The  yield  is  about 
60  to  70  •  per  cent. 

PREPARATION  OF  ETHYL  BROMIDE  (C2H5Br).i 
Sixty  grammes  of  bromine  are  slowly  added  to  a  mixture  of 
60  grm.  of  alcohol  and  10  grm.  of  red  phosphorus,  the  whole 

1  Meyer  u.  Jacobsen,  "  Lehrbuch  der  Organ,  Ch."  (1907), 
p.  281, 


HALOGEN  COMPOUNDS  69 

being  shaken  continually  and  well  cooled.  When  all  the 
bromine  has  been  added  the  mixture  is  shaken  mechanically 
for  some  hours,  and  then  distilled  from  the  water-bath.  The 
ethyl  bromide  which  distils  over  is  washed,  first  with  dilute 
sodium  carbonate  solution  and  then  several  times  with  water. 
It  is  dried  with  calcium  chloride  and  redistilled.  Colourless 
heavy  liquid  boiling  at  38°.  A  better  method  of  preparation 
is  given  on  p.  71. 

PREPARATION  OF  ETHYL  IODIDE  (C2H5I).i  Fifty 
grammes  of  iodine  are  slowly  added  in  small  portions  to  a 
mixture  of  5  grm.  of  red  phosphorus2  and  40  grm.  of  alcohol, 
the  whole  being  cooled  from  time  to  time  by  immersing  the 
flask  in  ice-water.  When  all  the  iodine  has  been  added,  the 
whole  is  set  aside  at  the  ordinary  temperature  over -night  and 
then  boiled  under  a  reflux  condenser  on  the  water -bath  for 
two  hours.  The  ethyl  iodide  is  distilled  off,  washed  with 
dilute  caustic  alkali,  and  then  several  times  with  water,  dried 
with  calcium  chloride,  and  redistilled.  Ethyl  iodide  forms 
a  colourless,  sweet-smelling  oil  which  boils  at  72 '3°.  On 
keeping,  it  gradually  acquires  a  violet  colour  owing  to  the 
separation  of  iodine.  Yield  95  to  98  per  cent. 

HALOGEN  ACID.  Hydriodic  acid  usually  reacts 
readily  with  alcoholic  hydroxyl  groups,  replacing  them 
by  iodine.  In  the  case  of  polyhydric  alcohols  only  one 
hydroxyl  is  thus  replaced,  the  others  being  reduced, 
e.g.  mannite,  C6H8(OH)6,  gives  a  mixture  of  hexyl 
iodides,  C6H13I.  Hydriodic  acid  also  reacts  with 
ethers,  giving  either  a  mixture  of  iodides,  or  the  alcohol 
of  the  higher  radical  and  iodide  of  the  lower,  according 
to  circumstances.  On  the  latter  reaction  is  based 
Zeisel's  estimation  of  methoxy-  and  ethoxy-groups. 
Hydrobromic  and  hydrochloric  acids  also  react  with 
alcoholic  hydroxyl,  but  less  readily.  In  the  case  of 
hydrochloric  acid  the  reaction  is  usually  so  incomplete 
that  it  is  necessary  to  assist  it  by  adding  a  dehydrating 

1  Loc.  cit. 

2  According  to  Walker  a  considerable  amount  of  time  can 
be  saved  by  using  a  mixture  of  equal  parts  of  red  and  yellow 
phosphorus.     Soc.  61,  717. 


yo        PREPARATION  OF  ORGANIC  COMPOUNDS 

agent,  such  as  zinc  chloride  or  sodium  sulphate.  The 
latter  of  these  substances  is  to  be  preferred,  as 
zinc  chloride  is  apt  to  cause  isomeric  change,  e.g. 
CH3(CH2)5CH2OH,  with  hydrochloric  acid  and  zinc 
chloride,  gives  CH3(CH2)4CHC1.CH3,  the  unsaturated 
hydrocarbon,  CH3(CH2)4CH  :  CH2,  being  formed  as  an 
intermediate  product.1 

Hydrochloric  acid  gas  is  best  prepared  by  the  action 
of  technical,  concentrated  sulphuric  acid  ("  mono- 
hydrate  "  or  "  B.O.V.")  on  sal-ammoniac  in  a  Kipp's 
apparatus.  Such  apparatus  should  not  be  shaken,  as 
sulphuric  acid  dissolves  some  hydrochloric  acid,  and 
on  agitation  this  is  apt  to  come  out  of  solution  suddenly 
and  project  the  concentrated  acid  from  the  top  of  the 
apparatus.  The  gas  can  also  be  obtained  by  dropping 
concentrated  sulphuric  acid  into  concentrated  hydro- 
chloric acid  or  a  mixture  of  this  latter  and  common 
salt.  If  generated  in  this  way  it  must  be  dried  by 
passing  through  strong  sulphuric  acid. 

Hydrobromic  acid  gas  is  most  readily  obtained  by 
the  action  of  hydrogen  sulphide  on  bromine  : 2 

H2S  -f-  Br2  =  2HBr  +  S. 

The  sulphuretted  hydrogen  is  obtained  from  a  Kipp's 
apparatus,  and  after  washing  is  passed  through 
bromine  contained  in  a  narrow  wash-bottle  and  covered 
with  a  layer  of  water.  The  evolved  gases  are  washed 
with  a  solution  of  potassium  bromide  in  which  some 
red  phosphorus  is  suspended.  A  rapid  stream  of 
almost  pure  hydrobromic  acid  can  thus  be  obtained. 
It  is  quite  free  from  bromine  vapours  and  sulphuretted 
hydrogen. 

PREPARATION  OF  HEXYL  IODIDE  (C6H13I).3  Sixty- 
seven  grammes  of  iodine  and  75  c.c.  of  water  are  placed  in  a 
tubulated  retort  the  neck  of  which  is  connected  with  a  sloping 
reflux  condenser.  Ordinary  phosphorus  is  then  added  in 
small  pieces  to  the  gently  warmed  mixture  until  a  colourless 
solution  is  obtained.  The  condenser  is  then  lowered  to  the 

1  B.  7,  1792.  2  C.  r.  no,  784.  3  B.  40,  142. 


HALOGEN  COMPOUNDS  71 

normal  position,  15  grm.  of  mannite  added  to  the  contents  of 
the  retort,  and  the  whole  distilled  fairly  rapidly  in  a  current 
of  carbon  dioxide,  led  in  by  a  tube  passing  through  the  tubulus. 
When  the  liquid  begins  to  become  coloured  owing  to  the  sepa- 
ration of  iodine,  the  distillation  is  interrupted,  the  contents 
of  the  retort  cooled,  and  more  phosphorus  added  until  the 
liquid  is  again  decolorised.  The  distillate,  together  with 
another  15  grm.  of  mannite,  is  returned  to  the  retort  and  dis- 
tilled as  before.  This  operation  is  repeated  once  again,  and 
finally  the  distillate  is  collected,  the  aqueous  layer  removed 
in  a  separating  funnel,  and  the  oil  washed  first  with  dilute 
soda  and  then  with  water.  It  is  dried  with  calcium  chloride 
and  redistilled.  The  greater  portion  passes  over  between 
165°  and  170°,  and  consists  of  a  mixture  of  isomeric  hexyl 
iodides.  These  can  be  partially  separated  by  repeated 
fractionation  under  reduced  pressure. 

PREPARATION  OF  ETHYL  BROMIDE  (C2H5Br).  Twenty- 
five  grammes  of  alcohol  are  added  to  50  grm.  of  concentrated 
sulphuric  acid  with  continual  shaking.  When  the  mixture  has 
cooled  it  is  poured  on  to  60  grm.  of  finely  powdered  potassium 
bromide,  and  the  whole  allowed  to  stand  over-night.  The 
mixture  is  then  distilled  from  the  water-bath  and  the  ethyl 
bromide  purified  as  described  on  p.  68. 

PREPARATION  OF  ETHYL  CHLORIDE.*  The  reaction 
is  carried  out  in  the  apparatus  shown  (Fig.  48).  One  hundred 
grammes  of  alcohol  and  50  grm.  of  fused  zinc  chloride  are 
placed  in  the  flask  A,  and  dry  hydrochloric  acid  gas  led  through 
the  boiling  mixture.  The  ethyl  chloride  formed  is  washed 
with  water  in  B  and  concentrated  sulphuric  in  c.  The  spiral 
condenser  D  is  surrounded  by  a  freezing  mixture  of  ice  and 
salt,  as  is  also  the  receiver  E.  As  ethyl  chloride  boils  at  12° 
it  must  be  preserved  in  thick,  sealed  glass  tubes.  The  yield 
is  almost  quantitative. 

THIONYL  CHLORIDE  (SOClg).  Thionyl  chloride 
serves  chiefly  for  the  preparation  of  acid  chlorides,2 
and  for  this  purpose  has  the  advantage  over  phos- 

1  B.  7,  741  ;  A.  174,  372  ;  J.  pr.  [2]  14,  195. 

2  B.  16,  1627  ;  37,  2951,  3217  ;  38,  605  ;  40,  2649;  M.  22, 
109. 


72        PREPARATION  OF  ORGANIC  COMPOUNDS 

phorus  pentachloride  that  aldehydic  and  ketonic 
groups  are  unaffected  by  it,  and  that  it  gives  rise  only 
to  gaseous  by-products  : 

SOC12  +  2R.COOH  =  S02  +  H20  +  2R.COC1. 
Any  excess    of   the   reagent   is   readily  removed  by 


FIG.  48. 

distillation  (B.P.  78°),  or  the  excess  can  be  destroyed 
by  adding  formic  acid  : 

SOC12  +  2HCOOH  =  SO2  +  2CO  +  2HC1  +  H2O. 

Thionyl  chloride  has  found  its  chief  use  in  the  pre- 
paration of  the  chlorides  of  complicated  amino-acids,1 

i  B.  36,  2094. 


HALOGEN  COMPOUNDS  73 

but  in  this  case  one  of  the  hydrogen  atoms  of 
the  amino -group  must  first  be  replaced  by  the 
carbethoxy  group  by  treatment  with  chlorcarbonic 
ester.  Otherwise  the  amino-group  will  also  be 
attacked.  It  has  also  proved  very  useful  for 
preparing  the  chlorides  of  the  pyridine  carboxylic 
acids.1 

Some  ketonic  acids,  such  as  pyruvic  acid,  do  not 
react  with  thionyl  chloride,  and  the  ^.-oxybenzoic 
acids  only  react  when  there  is  a  negative  group  in  the 
meta-position  to  the  carboxyl. 

Alcoholic  hydroxyl 2  is  also  sometimes  attacked  by 
thionyl  chloride,  e.g. : 

(C6H5CH2)(C6H5)(C2H5)COH     — 

-     (C6H6CH2)(C6H5)(C2H5)CC1. 

The  reaction  is  usually  carried  out  with  a  slight 
excess  of  thionyl  chloride  and  no  solvent,  and  either 
takes  place  at  the  ordinary  temperature  or  on  gentle 
warming. 

SULPHURYL  CHLORIDE  (SO2C12).  Sulphuryl  chloride 
is  but  little  used  in  the  laboratory,  but  is  employed  to 
a  large  extent  technically  for  preparing  acid  chlorides 
from  the  corresponding  salts 3  (cf.  p.  60).  The 
calcium  salts  give  the  best  results.  The  reaction 
takes  place  at  the  ordinary  temperature,  but  very 
intimate  mixing  is  required. 

CHLORSULPHONIC  ACID  (SO2OHC1).  Chlorsulphonic 
acid,  obtained  by  passing  dry  hydrochloric  acid  gas 
into  oleum,  is  chiefly  used  for  preparing  the  chlorides 
of  sulphonic  acids  directly  from  the  aromatic  hydro- 
carbons. A  large  excess  of  the  acid  is  used  and 
rise  in  temperature  prevented.  The  yields  are 
excellent.4 

1  M.  22,  III. 

2  B.  37,  1453. 

3  D.R.P.  151,864,  63,593. 

4  D.R.P.    98,030  ;    B.    12,    1848  ;    42,    1802,    2057.      This 
method  is   used    technically  for  the  preparation  of  toluene- 


74        PREPARATION  OF  ORGANIC  COMPOUNDS 

BENZENE  SULPHOCHLORIDE  l  and  CARBONYL 
CHLORIDE2  can  also  be  employed  for  replacing  hy- 
droxyl  by  chlorine.  The  latter  substance  also  reacts 
with  benzaldehyde  to  form  benzal  chloride : 

C6H6CHO  +  COC12  =  C6H5CHC12  +  CO2. 


(iv)  REPLACEMENT  OF  THE  DIAZO-GROUP 
BY  HALOGEN 

Most  primary  aromatic  amines  when  treated  with 
nitrous  acid  are  readily  converted  into  diazo-salts  :  3 

ArNH2  +  HNO2  +  HC1  =  ArN  :N.C1  +  H2O. 

The  diazo-compounds  when  isolated  are  exceedingly 
explosive,  but  numerous  methods  are  known  whereby 
the  diazo-group  can  be  replaced  by  other  groups  or 
elements  without  actually  isolating  the  explosive 
substance. 

For  replacing  the  diazo-group  by  halogen  three 
methods  are  known,  viz.  : 

(i)  Method  of  Griess.  This  consists  in  heating  the 
diazo-salt  with  the  halogen  acids.  The  method 
usually  goes  very  well  with  hydriodic  acid,  and  is 
the  standard  method  of  preparing  aromatic  iodides, 
but  is  far  less  satisfactory  with  the  other  halogen  acids. 

o.-sulphochloride,  an  intermediate  compound  in  the  manufac- 
ture of  saccharin  : 


— S02C1 
— CH3 


NHj 
— COOH 


NH 


Saccharin 

1  F.P.  328,120.  2  J.  pr.  [2]  i,  412. 

3  For  experimental  details  the  reader  is  referred  to  p.  238. 


HALOGEN  COMPOUNDS  75 

(ii)  Sandmeyer's  Method.  This  consists  in  treating 
the  diazo-salt  with  halogen  acid  and  cuprous  halide. 
It  is  of  very  general  application,  and  as  a  rule  gives 
excellent  results.  The  base  is  diazotised  in  the 
ordinary  way  (see  p.  238),  except  that  when  preparing 
bromine  or  iodine  compounds  it  is  best  to  replace 
the  hydrochloric  acid  by  sulphuric  acid.  The  resulting 
diazo-solution  or  suspension  is  then  slowly  run  into  a 
boiling  solution  of  the  cuprous  salt l  in  the  correspond- 
ing halogen  acid.  The  resulting  halogen  compound  is 
separated  by  steam  distillation  or  by  other  methods 
according  to  circumstances. 

(iii)  Gattermann's  Reaction.  This  consists  in  adding 
copper  powder  to  the  diazo-salt  of  the  corresponding 
halogen  acid.  The  reaction  takes  place  at  the  ordinary 
temperature  and  the  yields  are  as  good  as  or  better  than 
those  obtained  by  Sandmeyer's  method.  The  method 
has  the  advantage  that  less  bulky  solutions  have  to  be 
dealt  with.  For  the  preparation  of  the  copper  powder, 
zinc  dust  is  sifted  through  a  fairly  fine  sieve  into  a 
cold  saturated  solution  of  copper  sulphate  until  the 
latter  is  decolorised.  The  liquid  is  then  poured  off 
from  the  precipitated  copper  and  the  latter  washed 
once  or  twice  with  water.  It  is  then  shaken  up  with 
dilute  hydrochloric  acid  to  remove  excess  of  zinc  dust, 
and  when  no  more  hydrogen  is  evolved  the  acid  liquors 
are  poured  off  and  the  residue  washed  with  water  until 
neutral.  The  copper  powder  thus  obtained  is  very 
readily  oxidised  by  the  air  and  is  best  preserved 
as  a  paste  in  well-stoppered  bottles.  Instead  of  the 
powder  obtained  as  above,  the  commercial  copper 
bronze  can  be  used,  the  best  form  being  that  sold  by 
Kahlbaum  under  the  name  of  "  Naturkupfer  C." 
Before  use  this  should  be  freed  from  traces  of  oil  by 
washing  with  ether  or  ligroin. 

PREPARATION  OF  IODOBENZENE  (C6H5I).     (a)  Method 
of  Griess.2     Forty-eight  grammes  of  aniline  are  dissolved  in 

1  The  preparation  of  cuprous  chloride  and  cuprous  bromide 
will  be  found  described  on  p.  31.  2  A.  241,  35. 


76        PREPARATION  OF  ORGANIC  COMPOUNDS 

700  c.c.  of  water  and  85  c.c.  of  concentrated  hydrochloric  acid. 
Ice  is  added  until  the  temperature  falls  below  o°  and  the 
solution  diazotised  in  the  usual  way  with  a  solution  of  35  grm. 
of  sodium  nitrite,  the  temperature  being  kept  below  10°. 
A  cold,  concentrated  solution  of  85  grm.  of  potassium  iodide 
is  then  slowly  run  in  with  continual  stirring.  At  first  rapid 
evolution  of  nitrogen  takes  place,  but  towards  the  end  the 
reaction  becomes  less  vigorous  and  must  be  assisted  by  gentle 
warming  on  the  water-bath.  When  no  more  nitrogen  is 
evolved,  the  solution,  which  has  become  coloured  owing  to 
the  separation  of  iodine,  is  decolorised  by  the  addition  of 
caustic  soda,  the  heavy  oil  collected,  washed  with  water, 
and  steam-distilled.  The  oil  which  passes  over  is  collected, 
dried  with  calcium  chloride,  and  distilled.  lodobenzene 
forms  a  colourless,  heavy  oil  which  boils  at  1 88°.  Yield  almost 
quantitative. 

(b)  Gattermann's  Method.1  Thirty-one  grammes  of  aniline 
are  dissolved  in  400  grm.  of  50  per  cent,  sulphuric  acid,  and  the 
solution  cooled  below  o°  by  the  addition  of  ice.  The  aniline 
is  then  diazotised  as  usual  with  23  grm.  of  nitrite  in  concen- 
trated solution.  One  hundred  and  twenty-six  grammes  of 
potassium  iodide  and  40  grm.  of  copper  paste  or  powder  are 
then  added.  When  the  reaction  is  over  the  copper  sinks 
to  the  bottom  of  the  vessel.  The  iodobenzene  is  purified  as 
above.  Yield  70  per  cent. 

PREPARATION  OF  CHLOROBENZENE  (C6HsCl).  (a) 
Sandmeyer's  Method.  Thirty-one  grammes  of  aniline  are 
dissolved  in  200  c.c.  of  water  and  57  c.c.  of  concentrated 
hydrochloric  acid,  and  then  diazotised  in  the  ordinary  way 
with  23  grm.  of  sodium  nitrite  dissolved  in  60  c.c.  of  water. 
The  solution  thus  obtained  is  slowly  run  into  350  c.c.  of  an 
almost  boiling  10  per  cent,  cuprous  chloride  solution  prepared 
as  described  on  p.  31.  When  the  whole  has  been  added  the 
greater  part  of  the  aqueous  liquid  is  poured  off,  and  the  residual 
oil  steam-distilled.  The  oil  which  passes  over  is  collected, 
washed  with  dilute  sodium  carbonate,  then  with  water,  dried 
over  calcium  chloride,  and  finally  distilled.  Colourless  liquid 
boiling  at  132°.  Yield  73  per  cent. 

(b)  Gattermann's  Method.2  Thirty-one  grammes  of  aniline 
are  added  to  150  c.c.  of  water  and  225  c.c.  of  concentrated 

1  B.  23,  1222.  2  B.  23,  1220. 


HALOGEN  COMPOUNDS  77 

hydrochloric  acid.  Complete  solution  does  not  take  place. 
The  resulting  liquid  is  diazotised  as  before  with  23  grm.  of  nitrite. 
Forty  grammes  of  copper  paste  or  powder  are  added,  and  the 
whole  allowed  to  stand  until  the  reaction  is  over  (about  half 
an  hour).  When  this  is  the  case  the  copper  will  sink  to  the 
bottom  of  the  vessel.  The  chlorobenzene  is  purified  as  before. 
Yield  about  73  per  cent. 

o.-Chlortoluene  can  be  prepared  in  exactly  the  same 
way  as  the  above,  but  in  this  case,  whereas  Sandmeyer's 
method  gives  a  yield  of  only  30  per  cent.,  Gattermann's 
method  gives  a  yield  of  66  per  cent.  The  proportions 
to  use  are  :  36  grm.  o.-toluidine,  200  c.c.  cone.  HC1, 
150  c.c.  H2O,  23  grm.  NaNO2,  40  grm.  Cu  paste.  B.P. 
179°. 

PREPARATION  OF  BROMOBENZENE  (C6H5Br).i  ice  is 
added  to  130  grm.  of  concentrated  sulphuric  acid  until  the 
temperature  falls  to  o°.  Thirty-one  grammes  of  aniline  are 
then  added,  and  the  solution  diazotised  as  usual  with  23  grm. 
of  nitrite.  One  hundred  and  twenty  grammes  of  potassium 
bromide  and  40  grm.  of  copper  paste  are  then  added,  and,  when 
the  reaction  is  over,  the  bromobenzene  steam-distilled  off,  and 
purified  as  described  under  chlorobenzene.  Colourless  oil 
boiling  at  155°.  Yield  42  per  cent. 

PREPARATION  OF  o.-BROMBENZOIC  ACID  (C6H4[i] 
Br[2]COOH).2  Thirty -five  grammes  of  crystallised  copper 
sulphate,  100  grm.  of  sodium  bromide,  and  30  grm.  of  copper 
turnings  are  boiled  under  a  reflux  condenser  with  300  c.c.  of 
water  and  33  grm.  of  concentrated  sulphuric  acid  until  almost 
decolorised.  Forty  grammes  of  anthranilic  acid  are  then 
added  and  the  whole  allowed  to  cool.  Ice  is  added  until  the 
temperature  falls  to  o°,  and  then  a  cold,  concentrated,  aqueous 
solution  of  21  grm.  of  sodium  nitrite  slowly  run  in.  During 
the  addition  the  temperature  should  not  exceed  5°,  more  ice 
being  added  from  time  to  time  if  necessary.  When  all  the 
nitrite  has  been  added  the  whole  is  allowed  to  stand  over- 
night at  the  ordinary  temperature.  The  precipitated  o.- 
brombenzoic  acid  is  then  collected,  washed  with  cold  water, 
and  recrystallised  from  water.  It  forms  long  colourless 
needles  melting  at  147°-! 50°.  Yield  82  per  cent. 

1  B.  23,  1222.  2  A.  276,  56. 


78        PREPARATION  OF  ORGANIC  COMPOUNDS 

ADDENDA 

In  many  cases  when  halogen  compounds  are  being 
prepared  simultaneous  oxidation  takes  place.  The 
best-known  examples  of  this  are  the  preparation  of 
chloroform  and  iodoform  by  the  action  of  bleaching 
powder  or  hypoiodite  on  alcohol.  The  preparation 
of  chloranil  (see  p.  139),  and  of  chloropicrin,  C13CNO2, 
from  picric  acid  and  bleaching  powder  are  also  well- 
known  examples  of  simultaneous  oxidation  and  chlori- 
nation.  So  also  is  the  preparation  of  chloral,  CC13CHO, 
by  the  action  of  chlorine  on  alcohol. 

PREPARATION  OF  CHLOROFORM  (CHC18).  Two  hun- 
dred grammes  of  fresh  bleaching  powder  are  ground  up  to  a 
thin  cream  with  800  c.c.  of  water,  and  the  whole  then  trans- 
ferred to  a  large  flask  fitted  with  a  condenser.  Forty  grammes 
of  acetone  (or  alcohol)  are  then  added  and  the  whole  cautiously 
heated  until  the  reaction  sets  in.  The  flame  is  then  withdrawn 
until  the  frothing  ceases,  when  the  whole  is  distilled  until  no 
more  chloroform  comes  over.  The  lower  layer  of  the  distillate 
is  collected,  washed  with  dilute  caustic  soda,  dried  over 
calcium  chloride,  and  then  redistilled  from  the  water-bath. 
Heavy  colourless  liquid  with  a  sweet  smell.  B.P.  61°.  Yield 
about  40  grm. 

ACTION  OF  CHLORINE  ON  AROMATIC  IODO- 
COMPOUNDS.  When  chlorine  acts  on  aromatic  iodo- 
compounds  in  which  the  iodine  atom  is  attached 
directly  to  the  nucleus,  a  derivative  of  iodine  trichloride 
is  formed  in  which  the  iodine  is  trivalent.  Aliphatic 
iodine  compounds  or  compounds  in  which  the  iodine  is 
situated  in  a  side-chain  do  not  act  in  this  way. 

PREPARATION   OF   IODOBENZENE   BICHLORIDE 

(PhlCy.1  Twenty  grammes  of  iodobenzene  are  dissolved  in 
50  grm.  of  dry  chloroform  and  a  stream  of  dry  chlorine  passed 
into  the  liquid.  After  a  minute  or  two  pale  yellow  needles 
begin  to  separate.  When  these  no  longer  increase  in  quantity, 
they  are  filtered  off  and  washed  with  a  little  chloroform. 

1  J-  pr.  [2]  33,  155- 


HALOGEN  COMPOUNDS  79 

Yield  almost  quantitative.  The  compound  is  rather  unstable 
and  readily  loses  chlorine.  When  shaken  with  cold,  10  per 
cent,  caustic  soda  it  is  readily  changed  into  iodosobenzene l 
(C6H5I  :  O),  a  white  amorphous  mass  insoluble  in  all  the 
usual  solvents.  On  oxidation  (heating  to  100°  in  air 
or  boiling  with  water  in  a  current  of  air  or  oxygen)  it  gives 
iodoxybenzene  2  (C6H5IO2).  This  may  be  recrystallised  from 
water  or  glacial  acetic  acid  ;  it  explodes  violently  at  230°. 

REPLACEMENT  OF  THE  HALOGENS  BY  EACH 
OTHER.  Chlorine  or  iodine  can  be  replaced  by  bromine, 
(a)  By  treatment  with  cupric  bromide  3  in  alcoholic 
solution  : 

2CuBr2  +  2C3H5I  =  2C3H5Br  +  Cu2I2  +  Br2. 

In  order  to  remove  the  bromine  liberated  during  the 
reaction  some  copper  powder  is  added,  (b)  Sometimes 
treatment  with  bromine  is  sufficient,  e.g.  methylene 
iodide  treated  with  bromine  water  reacts  at  once  with 
the  evolution  of  heat  to  form  methylene  bromide  and 
iodine.4  (c)  Heating,  usually  under  pressure,  with 
boron  tribromide  often  gives  excellent  results.  In 
this  way  phosgene  is  converted  into  a  mixture  of 
COClBr  and  COBr2.5 

Bromine  and  iodine  can  be  replaced  by  chlorine, 
(a)  By  the  direct  action  of  chlorine  with  or  without  a 
solvent  (water,  chloroform,  &c.).  Thus  chlorine  reacts 
with  boiling  bromobenzene  to  form  chlorobenzene  and 
higher  halogenated  products.6  (b)  By  the  action  of 
antimony  pentachloride,  iodine  trichloride,  mercuric 
chloride,  or  best  silver  chloride.  Sometimes  the 
reaction  takes  place  in  the  cold,  sometimes  heating 
with  or  without  pressure  is  required.7 

1  It  should  be  noted  that  in  German  iodobenzene  (C6H6I)  is 
Jodbenzol,  whereas  PhIO2  is  Jodobenzol.      Iodosobenzene  is 
the  same  in  both  languages. 

2  B.  25,  3500  ;  26,  358.  3  A.  100,  124. 

4  A.  Ch.  30,  266.  5  C.  r.  120,  190. 

6  Z.  1868,  451  ;  B.  17,  795  ;  30,  1208. 

7  C.  r.  97,  1491  ;  A.  141,  207  ;  B.  22,  74. 


8o        PREPARATION  OF  ORGANIC  COMPOUNDS 

Chlorine  or  bromine  can  be  replaced  by  iodine  by 
treatment  with  hydriodic  acid,  or  the  iodides  of  alu- 
minium, boron,  calcium,  sodium,  or  potassium.  As 
aliphatic  iodine  compounds  are,  as  a  rule,  less  readily 
obtained  than  the  chlorine  or  bromine  analogues,  the 
method  is  often  useful.  Thus  carbon  tetrachloride  is 
readily  obtained  from  carbon  disulphide  and  chlorine, 
whereas  carbon  tetra-iodide  can  only  be  obtained 
conveniently  by  the  action  of  boron  tri-iodide  on  the 
tetrachloride.1 

The  most  convenient  method  of  replacing  chlorine 
or  bromine  by  iodine  is  by  treatment  with  sodium  or 
potassium  iodide2  in  aqueous,  or,  better,  in  alcoholic 
solution,  or  in  the  case  of  sodium  iodide,  in  acetone 
solution.  The  reaction  often  takes  place  at  once  with 
precipitation  of  sodium  chloride  or  bromide,  but  some- 
times requires  standing  and  warming.  The  bromine 
compounds  react  more  easily  than  the  chlorine  com- 
pounds, and  tertiary  more  easily  than  secondary  or 
primary. 

PREPARATION  OF  IODO ACETIC  ACID  (CH2ICOOH).3 
Twenty-five  grammes  of  chloracetic  acid  are  dissolved  in 
water  containing  42  grm.  of  potassium  iodide,  and  the  whole 
heated  on  the  water-bath  to  a  temperature  of  50°  for  two  to 
three  hours.  The  solution  is  then  decolorised  by  passing  in 
a  stream  of  sulphur  dioxide,  and,  after  cooling,  is  extracted 
with  ether.  The  ethereal  extract  is  shaken  with  calcium 
chloride  for  half  an  hour,  filtered,  and  then  the  ether  removed 
by  distillation.  The  crystalline  residue  is  recrystallised  from  a 
large  quantity  of  petroleum  ether,  best  by  means  of  a  Soxhlet 
apparatus.  Colourless  leaflets  melting  at  83°.  In  contact 
with  the  skin  it  causes  very  painful  blisters. 

PREPARATION  OF  CARBONYL  CHLORIDE  (Phosgene) 
(COC12)  .4  Phosgene  is  most  readily  obtained  in  the  laboratory 
by  the  action  of  strongly  fuming  sulphuric  acid  on  carbon 
tetrachloride.  Five  hundred  grammes  of  carbon  tetrachloride 

1  C.  r.  113,  19. 

2  A.  3,  266  ;  112,  125  ;  B.  29,  1558  ;  30,  2506  ;  43,  1528. 

3  B.  41,  2853,  4  B.  26,  1990. 


HALOGEN  COMPOUNDS 


81 


are  placed  in  a  flask  fitted  with  a  reflux  condenser  and  delivery 
tube,  as  shown  in  Fig.  49,  and  heated  to  boiling  on  a  water- 
bath.  About  1 20  c.c.  of  80  per  cent,  oleum  are  then  slowly 
dropped  in  through  the  tap  funnel,  the  end  of  which  has  been 
drawn  out  to  a  fine  point.  A  regular  stream  of  phosgene 
is  evolved  and  is  washed  by  passing  it  through  concentrated 


FIG.  49. 

sulphuric  acid.  This  acid  should  be  kept  cold  by  means  of 
cold  water  or  ice.  The  gas  can  be  collected  in  toluene  or  it 
can  be  liquefied  by  a  freezing  mixture.  When  all  the  oleum 
has  been  added  the  flask  is  warmed  for  five  minutes  over  a 
naked  flame.  The  yield  is  about  90  per  cent.  B.P.  8°. 


CHAPTER  IV 

THE  ALCOHOLS,  PHENOLS,  AND 
MERCAPTANS 

THE  number  of  methods  whereby  alcohols  and  phenols 
can  be  obtained  is  very  large,  and  only  those  which  are 
most  useful  for  preparing  these  compounds  in  the 
laboratory  will  be  considered. 

(i)  BY  THE  HYDROLYSIS  OF  THE  ESTERS. 
The  saponification  is  usually  carried  out  by  boiling  the 
ester  with  aqueous  or  alcoholic  caustic  alkali  solution. 
As  the  esters  of  organic  acids  are  usually  prepared  from 
the  alcohols,  the  method  is  of  little  importance  for 
preparative  purposes  except  in  the  case  of  the  higher 
alcohols,  which  are  obtained  by  saponifying  the  natu- 
rally occurring  waxes,  and  in  the  preparation  of  glyce- 
rine by  saponifying  the  vegetable  and  animal  oils  and 
fats  (soap  manufacture).  The  method  is,  however, 
of  great  importance  for  obtaining  alcohols  from  the 
esters  of  the  haloid  acids  (the  alkyl  and  aryl  halides) 
and  this  case  will  be  considered  in  a  separate  section. 

(ii)  FROM  THE  HALOGEN  COMPOUNDS.  In  the 
aliphatic  series  halogen  atoms  are  much  less  firmly 
bound  than  is  usually  the  case  in  the  aromatic  series, 
and,  as  a  rule,  can  be  replaced  by  hydroxyl  groups  by 
merely  boiling  with  water,  or  dilute  alkali,  or  alkali 
carbonate  solution.  If  the  carbon  atom  to  which  the 
halogen  is  attached  is  tertiary,  the  reaction  takes  place 
with  the  greatest  ease.  Thus  triphenyl  methyl  chloride 
is  decomposed  by  merely  warming  with  water.  The 
reaction  is  also  facilitated  when  more  than  one  halogen 
atom  is  attached  to  the  same  carbon  atom,  but  in  this 
case,  of  course,  the  products  of  hydrolysis  are  aldehydes, 

82 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        83 

ketones,  or  carboxylic  acids.     It  should  be  noted  that 
when  compounds  containing  the  structure 

Hlg 


are  hydrolysed,  the  product  is  not  the  corresponding 
unsaturated  alcohol,  but  the  tautomeric  ketone  : 

OH  v 

-    >CH-CO\ 

When  hydrogen  and  halogen  are  in  the  1.2-position, 
there  is  a  danger  of  a  simultaneous  loss  of  water  taking 
place  with  the  formation  of  an  unsaturated  compound  : 

\  /  \  /  \  / 

J>CH— CHlg    —    \CH  — C^-OH    —    OC—C/    +  H2O. 

For  this  reason  it  is  sometimes  found  best  to  bring 
about  hydrolysis  with  moist  silver  oxide,  or  to  convert 
the  halogen  compound  into  the  corresponding  acetate 
by  means  of  silver  acetate,  and  then  to  saponify  this 
with  as  mild  a  saponifying  agent  as  possible  : 

H-I-OH 
R| Hlg  AgiO. COCH3         —        RO.!COCH3 

_*        ROH  +  CH3C02H« 

The  saponification  of  the  halogen  compounds  is 
often  especially  useful  in  connection  with  the  Lederer- 
Manasse  synthesis,  and  will  be  further  discussed  in  this 
connection  on  p.  97. 

PREPARATION  OF  BENZYL  ALCOHOL  (C6H5CH2OH). 
Benzyl  chloride  is  boiled  under  a  reflux  condenser  with  10  parts 
of  a  10  per  cent,  potassium  carbonate  solution  until  the  smell 
of  the  chloride  has  disappeared  (about  twelve  hours).  After 
cooling,  the  whole  is  extracted  with  ether,  the  ether  extract 
dried  with  potassium  carbonate  or  sodium  sulphate,  and  then 


84        PREPARATION  OF  ORGANIC  COMPOUNDS 

distilled.     The  benzyl  alcohol  passes  over  at  206°  and  forms 
a  colourless  liquid.     See  also  pp.  97-100. 

PREPARATION  OF  GLYCOLLIC  ACID  (CH2OHCOOH) 1.1 
One  hundred  grammes  of  chloracetic  acid  are  dissolved  in 
800  c.c,  of  water,  and  the  solution  thus  obtained  boiled  under 
a  reflux  condenser  with  112  grm.  of  very  finely  ground  marble 
until  carbon  dioxide  is  no  longer  evolved  (two  to  three  days). 
On  cooling,  three  layers  of  crystals  are  usually  formed,  viz.  a 
top  layer  consisting  of  Ca(C2H3O3)2.4H2O  (microscopic  hair- 
like  needles),  a  middle  layer,  sometimes  absent,  consisting  of 
Ca(C2H3O3)2  (six-sided  rods),  and  a  bottom  layer  consisting  of 
CaClC2H3O3 .  3H2O  (octahedra).  The  flask  is  carefully  warmed 
without  shaking  until  the  top  layer  has  gone  into  solution, 
the  whole  filtered,  and  the  precipitate  boiled  out  several  times 
with  water.  The  united  filtrates  are  allowed  to  stand  for 
several  days,  when  crystallisation  usually  takes  place.  Should 
this  not  happen  the  solution  must  be  concentrated.  The 
crystals  are  filtered  off  and  well  pressed  down  in  order  to  free 
them,  as  far  as  possible  from  mother -liquor,  ground  up  with 
their  own  weight  of  cold  water,  and  again  filtered  and  pressed. 
This  treatment  is  continued  until  chloride  can  no  longer  be 
detected  in  the  filtrate.  The  yield  of  the  calcium  salt  is  about 
66  per  cent.  It  is  dried  in  the  air  or  by  pressing  between  filter- 
paper. 

In  order  to  obtain  the  free  acid,  the  calcium  salt  is  decomposed 
with  oxalic  acid,  and  as  any  excess  of  oxalic  acid  hinders  the 
crystallisation  of  the  glycollic  acid,  before  proceeding  it  is 
necessary  to  estimate  accurately  the  calcium  content  of  the 
above  salt.  The  calcium  is  then  precipitated  from  the  boiling 
solution  by  slowly  adding  the  calculated  quantity  of  oxalic 
acid  dissolved  in  boiling  water.  The  calcium  oxalate  is 
removed  by  filtration,  and  the  filtrate  concentrated  until  a 
crystallisation  sets  in.  On  cooling,  glycollic  acid  separates 
in  colourless  leaflets  which  melt  at  80°.  It  is  very  soluble  in 
water.  The  yield  is  about  75  per  cent,  of  theory  (reckoned  on 
the  calcium  salt). 

In  the  aromatic  series  the  halogen  atoms  are  very 

firmly  bound  and,  as  a  rule,  can  only  be  replaced  with 

the  greatest  difficulty.  Negative  substituents,  however, 

especially  nitro-groups,  in  the  ortho-  or  para-  position, 

1  B.  16,  2954. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        85 

render  the  halogen  atom  more  reactive.  Thus  picryl 
chloride  (syw.-trinitrochlorobenzene)  acts  as  a  true  acid 
chloride  (just  as  picric  acid  is  a  strong  acid),  and  is 
rapidly  hydrolysed  by  water.  In  the  naphthalene  and 
anthraquinone  derivatives  the  halogen  atom  is  more 
readily  replaced  than  is  the  case  in  the  benzene 
compounds.1 

PREPARATION  OF  2.4-DINITROPHENOL,  C6H3[i] 
OH[2.4](NO2)2-  Twenty  grammes  of  chlordinitrobenzene  are 
boiled  under  a  reflux  condenser  with  21  grm.  of  sodium 
carbonate  (anhydrous)  and  225  c.c.  of  water  until  complete 
solution  is  obtained.  After  cooling,  the  solution  is  acidified 
with  hydrochloric  acid  and  the  precipitated  dinitrophenol 
collected,  washed  with  cold  water,  and  dried  between  filter- 
paper  or  in  a  vacuum  desiccator.  It  melts  at  114°.  The  yield 
is  about  90  per  cent. 

(iii)  FROM  THE  SULPHONIC  ACIDS.  The  aro- 
matic sulphonic  acids  on  fusion  with  caustic  alkali  are 
converted  into  phenols,  and  this  forms  one  of  the  most 
important  methods  of  obtaining  the  phenols  both  in 
the  laboratory  and  on  the  large  scale.  Caustic  potash 
is  the  best  alkali  to  employ,  as  when  caustic  soda  is  used 
there  is  more  likelihood  of  simultaneous  oxidation 
taking  place.  In  some  cases  it  is  found  advantageous 
to  carry  out  the  reaction  by  heating  with  alcoholic 
caustic  potash  solution  under  pressure. 

In  the  case  of  di-  or  poly-sulphonic  acids,  one  or 
more  groups  can  be  replaced  by  carefully  regulating 
the  conditions  of  the  experiment.  Halogen  groups, 
if  present,  are  usually  simultaneously  replaced  by 
hydroxyl.  It  must  be  borne  in  mind  that  when 
polyhydric  phenols  are  heated  to  a  high  temperature 
with  caustic  alkali,  a  rearrangement  takes  place,  the 
hydroxyl  groups  taking  up  the  meta-  position  to  each 
other.  Hence  all  the  benzene  disulphonic  acids  when 
fused  with  potash  give  resorcinol. 

1  The  halogen  in  haloid  phenols  can  be  replaced  by  hydroxyl 
by  heating  under  pressure  with  alkaline  earth  hydroxides. 
Pat.  Anm.  Kl.  12.  q.  F.  31,351. 


'86   PREPARATION  OF  ORGANIC  COMPOUNDS 

In  the  naphthalene  series  the  method  is  very  im- 
portant for  preparing  the  technically  valuable  naphthol 
and  amino-naphthol  sulphonic  acids,  and  the  following 
general  rules  are  worth  remembering  : 

Sulphonic  groups  in  the  a-  position  are  more  readily 
replaced  than  those  in  the  ft-  position. 

When  a-naphthylamine-a-sulphonic  acids  are  fused 
with  caustic,  the  amino-group  is  only  unattacked  when 
on  a  different  ring  from  the  sulphonic  group.  If  on  the 
same  ring  it  is  replaced  by  hydroxyl. 

Of  the  a-naphthylamine-  or  a-naphthol-,  a-sulphonic 
acids,  the  sulphonic  group  in  the  peri-  position  is  the 
most  readily  replaced,  e.g. : 


S03H  OH 


OH  OH 


S0H 


S03H 


Of  the  a-naphthylamine-  or  a-naphthol-,  /5-sulphonic 
acids,  the  groups  in  the  epi-  or  kata-  positions  are  most 
readily  replaced,  e.g. : 


OH 


OH 


S03H 


S03H 


S03H 


OH 
HO/\/\ 


/\/SO,H 


S03H 


If  the  amino  or  phenolic  group  is  in  the  ft-  position, 
then  the  /3-sulphonic  groups  in  the  kata-  and  2.3- 
positions  are  the  most  readily  replaced. 

In  carrying  out  the  fusion  the  caustic  potash  (from 
1 1  to  15  parts)  is  melted  in  a  nickel  basin  with  a  little 
water,  the  sulphonic  acid  gradually  added,  and  the 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        87. 

whole  well  stirred  with  a  thermometer  which  is  pro- 
tected from  the  action  of  the  alkali  by  a  tube  of  metal 
or  hard  glass,  the  annular  space  round  the  bulb  being 
filled  for  preference  with  mercury  or  paraffin  wax. 

PREPARATION  OF  PHENOL  (C6H5OH)  .*  Thirty  grammes 
of  caustic  potash  and  about  5  c.c.  of  water  are  melted  at  a 
low  temperature  in  a  nickel  basin,  and  then  20  grm.  of  potassium 
benzene  sulphonate  added  and  stirred  in.  The  temperature 
is  then  raised  to  252°  and  maintained  at  this  point  for  one 
hour.  After  cooling,  the  melt  is  dissolved  in  a  little  water 
and  then  acidified  with  concentrated  hydrochloric  acid,  care 
being  taken  not  to  allow  the  solution  to  get  too  hot,  as  in  that 
case  considerable  quantities  of  phenol  will  be  lost  by  volatili- 
sation. The  solution  is  then  extracted  several  times  with 
ether,  the  ethereal  extract  dried  with  anhydrous  sodium 
sulphate,  and  the  ether  removed  by  distillation.  The  residual 
phenol  passes  over  at  about  1 80°  and  solidifies  in  the  receiver. 
Colourless  needles.  M.P.  42°.  B.P.  182°.  Yield  96  per 
cent. 

PREPARATION  OF  a-  AND  /3-NAPHTHOL  (C10H7OH). 
Thirty  parts  of  caustic  soda  and  i  part  of  water  are  fused  in 
a  nickel  basin  and  heated  to  280°.  Ten  parts  of  sodium 
naphthalene  a-  or  /3-sulphonate  are  slowly  added,  and  the 
temperature  raised  to  300°,  and  then  to  3io°-32O°  for  ten 
minutes.  After  cooling,  the  melt  is  dissolved  in  water, 
acidified  as  above  with  hydrochloric  acid,  the  naphthol  filtered 
off  from  the  cold  solution,  washed,  and  recrystallised  from  water. 
a-Naphthol  melts  at  95°;  /3-naphthol  at  122°.  Yields  about 
80  per  cent. 

(iv)  BY  GRIGNARD'S  METHODS.  When  a  halogen 
compound,  preferably  the  iodide,  is  treated  in  absolute 
ethereal  solution  with  magnesium,  a  magnesium  alkyl 
or  aryl  compound  is  formed : 

R.Hlg  +  Mg  =  MgRHlg. 

To  obtain  a  carbinol  from  this  it  may  be  allowed  to 
react  on  a  variety  of  compounds,  of  which  the  following 
may  be  mentioned  : 

1  J-pr.  [2]  17,  394;  20,300. 


88        PREPARATION  OF  ORGANIC  COMPOUNDS 
Oxygen  and  water  : 

RMgl  +  O  +  H20  =  R.OH  +  MglOH. 
Aldehydes  : 

RMgl  +  R'.CHO=  R'CHOHR  +  MglOH. 
Ketones : 

RMgl  +  R'R"CO  =  RR'R"COH  -f  MglOH. 

And  a  similar  reaction  takes  place  with  acid  chlorides, 
acid  anhydrides,  &c. 

PREPARATION  OF   PHENYL  METHYL  CARBINOL 

(C6H5CHOHCH3).i  The  ether  used  in  this  experiment  must 
be  pure  and  perfectly  dry  (distil  over  sodium  or  phosphorus 
pentoxide),  and  all  apparatus  must  be  scrupulously  dry. 

Thirty-six  grammes  of  methyl  iodide  are  dissolved  in  50  c.c. 
of  absolute  ether,  and  20  c.c.  of  the  mixture  added  to  6  grm.  of 
clean  magnesium  ribbon  in  a  dry  flask  provided  with  a  reflux 
condenser.  If  a  brisk  reaction  does  not  set  in  at  once  it  may  be 
started  by  adding  a  trace  of  iodine.  When  the  reaction  has 
subsided,  70  c.c.  of  absolute  ether  are  added  and  then  the 
rest  of  the  iodide  solution  drop  by  drop.  The  whole  is  boiled 
for  half  an  hour,  a  little  more  methyl  iodide  being  added,  if 
necessary,  to  complete  the  solution  of  the  magnesium.  The 
whole  is  then  cooled  by  surrounding  with  ice,  and  a  solution 
of  26  grm.  of  benzaldehyde  in  its  own  volume  of  absolute  ether 
added  slowly  with  constant  shaking.  After  standing  over- 
night the  flask  is  cooled  with  water,  and  dilute  hydrochloric 
acid  added  slowly  until,  on  shaking,  the  whole  of  the  solid 
matter  dissolves  (250  c.c.  of  2N  acid).  The  ethereal  layer  is 
then  removed,  washed  first  with  sodium  bicarbonate  solution, 
then  with  sodium  bisulphite  (to  remove  iodine),  and  again 
with  sodium  bicarbonate.  It  is  dehydrated  over  potassium 
carbonate,  the  ether  removed  by  distillation,  and  the  carbinol 
distilled  in  vacua.  It  boils  at  100°  at  15  mm.  The  yield  is 
about  65  per  cent. 

(v)  FROM  THE  AMINES.  This  replacement  is  of 
great  importance  in  the  aromatic  series,  and  may  be 
carried  out  either  directly  or  indirectly. 

1  Cohen,  "  Practical  Organic  Chemistry  "  (1908),  p.  206. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        89 

As  a  rule,  amino-groups  are  only  replaced  by  hydroxyl 
groups  by  the  action  of  caustic  alkali  when  a  negative 
substituent,  such  as  a  nitro-group,  is  in  the  ortho-  or 
para-  position.  Thus  aniline  on  boiling  with  caustic 
alkali  gives  no  trace  of  phenol,  whereas  the  nitrophenol 
is  readily  obtained  in  good  yield  by  boiling  ortho-  and 
/>tfnz-nitraniline  with  caustic  potash.1 

Secondary  and  tertiary  bases  having  a  nitroso-group 
in  the  para-  position  also  easily  give  the  nitroso-phenol 
(see  p.  196). 

In  the  naphthalene  series  amino-groups  are  more 
readily  replaced,  e.g.  a-naphthylamine  salts  on  heating 
with  water  to  200°  give  a-naphthol. 

A  more  important  method,  and  one  which  has  been 
applied  technically  for  the  preparation  of  some  of  the 
naphthol  sulphonic  acids,  consists  in  heating  the 
amino-compound  with  sodium  bisulphite.  Under  these 
circumstances  a  sulphite  ester  is  first  formed,  which  is 
then  hydrolysed  to  the  corresponding  phenol : 

ArNH2     —      ArO.SO2H     —      ArOH. 

The  reaction  takes  place  most  readily  with  a-naph- 
thylamine sulphonic  acids. 

PREPARATION    OF    i-NAPHTHOL-4-SULPHONIC    ACID 

(Neville  and  Winther's  Acid).2  Thirty -two  grammes  of  sodium 
naphthionate,  20  c.c.  of  water,  and  75  c.c.  of  sodium  bisulphite 
solution  (40°  Be.)  are  heated  for  twenty-four  hours  with 
continual  stirring  to  85°-9O°.  After  cooling,  the  solution  is 
acidified  with  hydrochloric  acid  (use  Congo  paper)  and  unchanged 
naphthionic  acid  filtered  off  (about  3  to  4  grm.).  The  ni- 
trate is  made  alkaline  with  caustic  soda  and  boiled  until  no 
more  ammonia  is  evolved.  It  is  then  again  acidified  with 
hydrochloric  acid  and  boiled  until  the  smell  of  sulphur  dioxide 
has  vanished.  Finally,  the  required  sulphonic  acid  is  precipi- 
tated as  its  sodium  salt  by  saturating  the  hot  solution  with 
common  salt. 

The  indirect    replacement   of    the   amino-group   is 
*  B.  7,  77.  a  D.R.P.  109,102. 


90        PREPARATION  OF  ORGANIC  COMPOUNDS 

brought  about  by  boiling  solutions  of  the  diazo- 
salts  : 

ArN  :  NHSO4  +  H2O  =  ArOH  +  H2SO4  +  N8. 

This  method  is  also  applicable  to  the  aliphatic  series, 
but  as  the  aliphatic  diazo-compounds  are  not  formed 
by  the  action  of  nitrous  acid  on  the  primary  amines,  it  is 
only  necessary  to  add  sodium  nitrite  to  an  acid  solution 
of  the  base  : 

R.NH2  +  HO2N  =  R.OH  +  N2  +  H2O. 

As  a  preparative  method,  the  reaction  is  not  much 
applied  except  in  the  aromatic  series. 

As  the  diazo-sulphates  give  the  best  yield  of  the 
phenol,  it  is  usual  to  use  sulphuric  acid  for  diazotising. 
The  diazo-salt  is  not  isolated,  but  its  solution  either 
heated  to  boiling  or  slowly  added  to  boiling,  dilute 
sulphuric  acid,  and  the  whole  boiled  until  no  more 
diazo-compound  is  present  (test  with  an  alkaline 
solution  of  R-salt  or  /3-naphthol) .  The  yields  in  some 
cases,  especially  with  amino-phenols,  are  very  poor, 
but  can  often  be  improved  by  boiling  the  diazo-sulphate 
with  copper  sulphate. 

PREPARATION  OF  DI-£.-OXYDIPHENYL  (HO.C6H4. 
CsH^.OH).1  Fifty  grammes  of  benzidine  are  dissolved  in  a 
litre  of  water  and  60  c.c.  of  concentrated  hydrochloric  acid. 
The  solution  is  diluted  to  5  litres,  200  grm.  of  concentrated 
sulphuric  acid  added,  and  the  whole  diazotised  in  the  usual 
way  (see  Chapter  XI)  with  a  solution  of  37  grm.  of  sodium 
nitrite  in  200  c.c.  of  water.  The  clear  solution  is  then  heated 
to  boiling  by  blowing  in  steam,  and  maintained  at  this  tempera- 
ture until  a  sample  gives  no  colour  with  alkaline  R-salt  solu- 
tion (about  twenty  minutes).  The  solution  is  filtered  hot, 
and  the  diphenol  crystallises  out  on  cooling.  It  forms  colour- 
less needles  melting  at  272°.  Yield  80  per  cent. 

PREPARATION  OF  PYROCATECHOL  (C6H4[i.2](OH)2).2 
Fifty  grammes  of  o.-amino  phenol  are  diazotised  in  the  ordinary 
way  and  the  diazo-solution  slowly  run  into  100  c.c.  of  boiling, 

i  B.  22,  335.  2  D.R.P.  167,211. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        91 

10  per  cent,  copper  sulphate  solution.  When  the  reaction  is 
complete  the  solution  is  cooled  and  the  pyrocatechol  extracted 
with  ether.  Hydroquinone  is  obtained  from  £.-amino  phenol, 
and  o.-cresol  from  o.-toluidine  in  exactly  the  same  way, 
except  that  for  50  grm.  of  amine  a  solution  of  200  grm.  of 
crystallised  copper  sulphate  in  its  own  weight  of  water  should 
be  used. 

If  a  diazo-nitrate  is  boiled  with  water,  nitration  takes 
place  simultaneously  in  the  ortho-  position. 

PREPARATION  OF  s-NITRO-CRESOL  (C6H3[i]CH3[3] 
NOa^jOH).1  Seventy-five  grammes  of  £.-toluidine  are  dis- 
solved by  gently  warming  in  380  c.c.  of  water  and  93  grm. 
of  nitric  acid  (D  =  i'33).  The  whole  is  then  cooled  below 
o°  (crystallisation  takes  place,  but  this  does  not  interfere 
with  the  reaction)  and  diazotised  in  the  usual  way  with 
a  solution  of  49  grm.  of  sodium  nitrite  in  100  c.c.  of  water. 
During  the  diazotisation  the  temperature  must  not  exceed 
10°.  After  standing  for  two  hours  at  a  low  temperature, 
about  100  c.c.  of  the  solution  are  transferred  to  a  litre  flask 
and  slowly  heated  to  boiling  under  a  reflux  condenser.  A  very 
violent  reaction  sets  in,  and  unless  a  very  efficient  condenser  is 
used,  considerable  quantities  of  the  nitro-cresol  will  be  lost. 
When  the  reaction  is  over,  the  rest  of  the  diazo-solution  is 
slowly  dropped  in  by  means  of  a  dropping-funnel.  When 
the  whole  has  been  added,  the  boiling  is  continued  for  a  few 
minutes,  and  the  nitro-cresol  then  distilled  over  with  steam. 
It  usually  collects  in  the  receiver  as  an  oil  which  soon  solidifies 
to  a  yellow  crystalline  mass.  M.P.  36-5°.  Yield  60  to  70  per 
cent. 

(vi)  BY  THE  REDUCTION  OF  THE  ALDEHYDES 
AND  KETONES.  A  very  large  number  of  reducing 
agents  have  been  employed  for  reducing  the  aldehydes 
and  ketones  to  the  corresponding  primary  and  secon- 
dary alcohols.  The  best  results,  however,  are  usually 
obtained  with  sodium  and  alcohol,  sodium  amalgam 
and  water,  aluminium  amalgam  and  water,  zinc 
dust  and  caustic  soda  or  ammonia,  or  zinc  dust  and 
glacial  acetic  acid.  Of  these  the  most  generally  used 

1  B.  24,  1960. 


92         PREPARATION  OF  ORGANIC  COMPOUNDS 

is  sodium  amalgam,  and  the  reduction  is  usually  carried 
out  by  dissolving  the  ketone  in  moist  ether  and  then 
shaking  with  the  amalgam.  Instead  of  ether,  benzene 
can  be  used,  small  quantities  of  water  being  added 
from  time  to  time,  or  the  amalgam  can  be  allowed 
to  act  on  the  moist  ketone  without  employing  a 
solvent. 

The  reduction  with  sodium  and  alcohol,  which  is 
particularly  useful  in  the  aromatic  series,  is  carried 
out  by  dissolving  the  ketone  (i  part)  in  alcohol  (10 
parts)  and  then  slowly  adding  sodium  wire  (i  part). 

Other  methods  applicable  to  special  cases  will  be 
found  discussed  at  the  end  of  this  section. 

The  reduction  of  the  ketones  is  usually  accompanied 
by  intermolecular  condensation,  a  pinacone  (ditertiary 
glycol)  being  formed  : 

2(CH3)2.CO  +  2H  =  (CH3)2.COH.COH.(CH3)2. 

Acetone  Pinacone 

In  the  aliphatic  series  the  pinacone  is  invariably 
formed  to  a  greater  or  less  extent,  but  by  choosing 
suitable  conditions  the  aromatic  ketones  can  usually 
be  reduced  without  any  pinacone  formation.  As  a 
rule,  pinacone  formation  takes  place  with  greater  ease 
when  an  acid  reducing  agent  is  used  than  when  the 
reduction  is  carried  out  in  alkaline  solution. 

PREPARATION  OF  METHYL   PHENYL  CARBINOL 

(CH3 .  CHOH .  C6H5)  .*  Twenty  grammes  of  acetophenone  are 
dissolved  in  200  grm.  of  alcohol  and  the  whole  warmed  on  the 
water-bath.  Twenty  grammes  of  sodium  are  rapidly  added, 
and  when  this  has  dissolved,  the  solution  neutralised  by 
passing  in  a  current  of  carbon  dioxide.  The  whole  is  then 
diluted  with  about  250  c.c.  of  water  and  the  alcohol  removed 
as  far  as  possible  by  distillation  from  the  water-bath.  The 
residue  is  extracted  with  ether,  the  ether  distilled  off,  and  the 
residue  distilled  in  vacuo.  The  carbinol  passes  over  at  118° 
at  40  mm.  or  at  100°  at  1 5  mm.  At  atmospheric  pressure  it 
boils  at  198°.  The  yield  is  about  40  per  cent. 

1  B.  31.  1003. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS       93 

PREPARATION  OF  BENZHYDROL  (C6H5)2CHOH.i 
One  part  of  benzophenone  is  dissolved  in  10  to  20  parts  of 
alcohol  and  about  5  parts  of  concentrated,  aqueous,  caustic 
potash.  Five  to  ten  parts  of  zinc  dust  are  then  added,  and  the 
whole  allowed  to  stand  in  a  warm  place  for  five  to  seven  days . 
The  solution  is  then  saturated  with  carbon  dioxide,  filtered,  and 
the  filtrate  evaporated  until  crystallisation  sets  in.  On  cooling, 
the  benzhydrol  separates  out  in  colourless  needles  which  melt 
at  68°.  The  yield  is  about  70  per  cent. 

PREPARATION  OF  BENZPINACONE,  (C6H5)2.COH.COH 
(C6H5)2.2  One  part  of  benzophenone,  2  parts  of  zinc  foil, 
and  10  parts  of  85  per  cent,  acetic  acid  are  boiled  for  fifteen 
minutes,  the  whole  being  well  shaken  at  frequent  intervals. 
The  liquid  is  then  poured  off  from  the  unattacked  zinc,  cooled, 
and  filtered.  The  filtrate  is  again  boiled  up  with  zinc,  and  this 
process  repeated  a  third  time,  the  solutions  being  filtered 
through  the  same  filter  each  time.  Finally  the  benzpinacone  is 
washed  with  acetic  acid  (5  acid  :  i  water)  and  then  recrystal- 
lised  from  13  parts  of  boiling  glacial  acetic  acid.  It  melts 
with  decomposition  at  168°.  The  yield  is  90  per  cent. 

The  a-diketones  are  best  reduced  with  zinc  dust  and 
sulphuric  acid,  iron  and  acetic  acid,  stannous  chloride 
and  hydrochloric  acid,  or  sodium  hydrosulphite  in 
alcoholic  solution.3 

PREPARATION  OF  HYDROBENZOIN  (C6H5CHOH. 
CHOHC6H5).4  Twenty  grammes  of  benzoin  are  dissolved  in 
200  c.c.  of  alcohol  and  the  solution  heated  on  the  water-bath 
with  22  grm.  of  stannous  chloride  in  60  c.c.  of  hydrochloric 
acid  (D  ==  1*17)  until  decolorised  (about  half  an  hour).  The 
whole  is  then  cooled,  filtered,  and  the  precipitate  washed  with 
a  little  alcohol.  M.P.  134°.  Colourless  leaflets  from  glacial 
acetic  acid  or  aqueous  alcohol.  Yield  almost  theoretical. 

The  indigoid  and  anthraquinonoid  dyes  are  best 
reduced  to  their  hydroxy  compounds  (the  "  vats  ")  by 

1  J-  pr.  [2]  33,  184. 

2  B.  14.  R.  1402.  C.  1881,  150. 

3  J-pr.  [2]  76,  137. 

4  B.  37,  1677. 


94        PREPARATION  OF  ORGANIC  COMPOUNDS 

treatment  with  alkaline  sodium  hydrosulphite.  The 
reduction  compounds  are  difficult  to  isolate  in  a  pure 
state,  as  they  are  very  rapidly  oxidised  by  the  air.1 
If,  however,  the  reduction  is  carried  out  with  zinc 
dust  and  boiling  acetic  anhydride  in  the  presence  of 
anhydrous  sodium  acetate,  the  vats  can  be  readily 
isolated  in  the  form  of  their  stable  acetic  esters. 

PREPARATION     OF    DIACETYLOXYANTHRANOL,2 
C.OCOCH3 

y    \C6H4.     One   part   of   anthraquinone    is   boiled    for 

C.OCOCH3 

a  short  time  with  10  to  15  parts  of  acetic  anhydride,  2,  parts 
of  anhydrous  sodium  acetate,  and  3  parts  of  zinc  dust.  The 
solution  after  cooling  is  filtered,  the  residue  dissolved  in  a  little 
boiling  glacial  acetic  acid,  filtered  hot,  and  the  filtrate  allowed 
to  cool.  The  diacetyl-oxyanthranol  is  collected,  and  recrystal- 
lised  several  times  from  glacial  acetic  acid.  It  forms  colourless 
needles  which  melt  at  260°. 

The     more     fully     reduced     anthraquinones,     the 
anthranols, 

,CH  . 

C6H  /  |        >C6H4 
XCOH/ 

are  more  stable  than  the  oxy  anthranols. 

/CH  . 

PREPARATION     OF    ANTHRANOL,   C6H4<(  >C6H4. 

\/ 


(a)  3  Ten  grammes  of  anthraquinone  are  boiled  with  400  c.c. 
of  glacial  acetic  acid  and  25  grm.  of  granulated  zinc.  Con- 
centrated hydrochloric  acid  is  added  to  the  boiling  liquid  in 
quantities  of  a  few  cubic  centimetres  at  a  time  until  further 
addition  no  longer  causes  the  appearance  of  a  transitory  brown 
colour  and  hydrogen  is  continuously  evolved.  The  reduc- 
tion requires  about  a  quarter  of  an  hour,  and  on  cooling  the 
solution  should  not  deposit  crystals.  When  cold,  the  whole 

1   Vide  J.  pr.  [2]  76,  141,  and  D.R.P.  204,568  (indigo  white)  ; 
B.  40,  390,  924.  2   B.  21,  1172. 

3  B.  20,  1854. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS       95 

is  poured  into  dilute  hydrochloric  acid,  and  the  precipitate 
recrystallised  from  glacial  acetic  acid.  Colourless  needles 
melting  with  decomposition  at  i63°-i7O°.  Yield  80  per 
cent. 

(b)  l  Ten  grammes  of  anthraquinone  are  dissolved  in  150  grm. 
of  concentrated  sulphuric  acid,  and  25  grm.  of  aluminium 
powder  ("  aluminium  bronze ")  slowly  added,  care  being 
taken  that  the  temperature  does  not  rise  above  3o°-4O°. 
When  almost  colourless,  the  solution  is  poured  into  i  litre 
of  water  and  the  precipitate  collected  and  recrystallised  from 
glacial  acetic  acid. 

Instead  of  aluminium  powder,  copper  powder  may  be  used 
(10  parts  anthraquinone,  160  H2SO4,  7  Cu  at  20°  to  40°). 

In  order  to  avoid  oxidation  when  crystallising  anthranol, 
it  is  advantageous  to  add  a  little  hydrochloric  acid  and  a  trace 
of  aluminium  powder  to  the  acetic  acid. 

The  true  quinones  are  usually  reduced  by  sulphurous 
acid,  but  are  more  rapidly  attacked  by  hydroxylamine 
or  phenylhydrazine.  The  latter  reagent  reduces 
alcoholic  solutions  of  quinone  with  almost  explosive 
violence. 

PREPARATION  OF  HYDROQUINONE  (Quinol) 

(C6H4[i.4](OH)2).2  For  this  preparation  either  pure,  very 
finely  ground  quinone  suspended  in  water,  or,  more  usually, 
the  suspension  of  crude  quinone  obtained  by  the  oxidation  of 
aniline  as  described  on  p.  138  is  used.  In  either  case  the  cold 
liquid  is  saturated  with  gaseous  sulphur  dioxide  until  it 
retains  the  smell  of  the  gas  after  standing  over-night.  The 
solution  is  then  extracted  several  times  with  ether,  the  ether 
removed  by  distillation,  and  the  residue  recrystallised  from 
water  containing  sulphurous  acid  and  animal  charcoal.  The 
hydroquinone  forms  colourless  needles  which  melt  at  169°. 

In  the  above  reduction  the  first  product  is  the  highly 
coloured  quinhydrone  (see  p.  103),  which  is  then  further  reduced 
by  the  sulphurous  acid  to  the  quinol. 

Aromatic  aldehydes,  in  which  the  aldehydic  group 
is  directly  attached  to  the  nucleus,  undergo  simul- 
taneous reduction  and  oxidation  when  heated  with 

1  D.R.P.  201,542.  2  A.  215,  127. 


96       PREPARATION  OF  ORGANIC  COMPOUNDS 

aqueous  caustic  alkali,  an  alcohol  and  a  carboxylic  acid 
being  formed  : 

2ArCHO  +  KOH  =  ArCH2OH  +  ArCOOK. 

(vii)  FROM    THE    UNSATURATED    COMPOUNDS. 

The  unsaturated  compounds  may  be  converted  into 
hydroxyl  compounds  by  the  addition  of  water,  hypo- 
chlorous  acid,  &c.,  or  by  oxidation. 

The  addition  of  the  elements  of  water  can,  in  some 
cases,  be  effected  in  the  presence  of  acids  or  alkalis, 
but  the  reaction  only  takes  place  with  great  difficulty 
in  the  case  of  ethylenic  compounds,  and  will  not  be 
further  considered.  It  may  be  remarked,  however, 
that  the  addition  takes  place  most  readily  when  the 
double  bond  is  adjacent  to  a  carboxyl  group. 

The  addition  takes  place  somewhat  more  readily  in 
the  case  of  acetylenes.  Thus  acetylene  itself  when 
passed  into  concentrated  or  dilute  sulphuric  acid  gives 
acetaldehyde  : 

H2O  Tautomeric 

CHjCH    —    CH2:CHOH    —    CH3.CHO. 

change 

Attempts  have  been  made  to  apply  this  reaction  to 
the  production  of  acetaldehyde  on  the  large  scale,  in 
order  to  obtain  ethyl  alcohol  by  its  reduction.  Such 
attempts,  however,  have  not  been  commercially 
successful.  As  certain  metals,1  such  as  platinum,  and 
some  salts,2  notably  mercury  salts,  act  as  catalysts  in 
the  above  reaction,  it  is  not  impossible  that  it  may 
become  commercially  successful  at  a  future  date. 

Of  greater  importance  than  the  above  addition  re- 
actions is  the  oxidation  of  ethylenic  bonds  to  vic-dioxy- 
compounds.  The  oxidation  is  usually  carried  out  by 
very  dilute  (i  to  2  per  cent.)  potassium  permanganate 
solution.  In  some  cases  alkali-hypobromites,  ferric 
chloride  in  acetone  solution,  Caro's  acid  (p.  193),  or 
nitric  acid  can  be  used.  Potassium  permanganate, 
however,  usually  gives  the  best  results. 

i  C.   1095  I,  1585.  2  B.  14,  1540. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS       97 

PREPARATION      OF      /3-PHENYL      GLYCERIC      ACID 

(C6H5.CHOH.CHOH.COOH).i  Sixty  grammes  of  cinnamic 
acid  are  dissolved  in  5  to  6  litres  of  water  and  the  solution 
made  strongly  alkaline  with  sodium  carbonate  or  caustic 
soda.  It  is  then  cooled  with  ice,  and  treated  slowly,  and  with 
continual  stirring  and  cooling,  with  90  grm.  of  potassium 
permanganate  in  2  per  cent,  aqueous  solution.  During  the 
oxidation  the  temperature  should  not  rise  above  o°.  The 
solution  is  filtered  from  precipitated  manganese  hydroxide, 
and  dilute  hydrochloric  acid  added  to  the  clear  filtrate  until  it 
is  only  slightly  alkaline.  It  is  then  boiled  down  to  about 
half  its  volume,  neutralised  with  hydrochloric  acid,  and 
concentrated  on  the  water-bath  to  a  small  volume.  A  good 
deal  of  salt  separates  out,  but  this  does  not  interfere  with  the 
isolation  of  the  acid.  After  cooling,  the  solution  is  repeatedly 
extracted  with  ether  (eight  to  ten  times) .  The  ethereal  extracts 
are  extracted  with  cold  water  and  the  dissolved  ether  removed 
from  the  aqueous  portion  by  blowing  air  through  it.  A  slight 
precipitate  separates  and  is  discarded.  The  filtrate  is  heated 
almost  to  boiling  and  neutralised  with  chalk.  On  cooling,  the 
calcium  salt  of  /3-phenyl  glyceric  acid  separates  out  and  is 
purified  by  recrystallisation.  The  free  acid  can  be  obtained 
by  decomposing  the  calcium  salt  with  hydrochloric  acid  and 
then  extracting  with  ether.  As,  however,  the  acid  is  very 
soluble  in  water  and  only  slightly  soluble  in  ether,  it  is  better 
to  decompose  the  calcium  salt  with  the  exact  amount  of 
oxalic  acid,  filter  off  the  calcium  oxalate,  and  concentrate 
the  filtrate  until  crystallisation  sets  in.  The  acid  crystallises 
from  water  in  colourless  needles  which  melt  with  decomposition 
at  141°. 

(viii)  FROM  THE  ALDEHYDES  BY  CONDENSA- 
TIONS, (a)  The  aldol  condensation  is  discussed  on 
p.  117,  and,  therefore,  it  is  merely  necessary  to  point  out 
that  if  the  condensation  is  carried  out  in  the  presence 
of  magnesium  amalgam,  the  aldehydic  group  of  the 
aldol  is  simultaneously  reduced,  a  dihydric  alcohol 
resulting. 

(b)  The  benzoin  condensation  is  discussed  on  p.  131, 
and  leads  to  aromatic  ketonic  alcohols. 

(c)  The  Lederer-Manasse  synthesis  is  of  considerable 

1  B.  21,  919  ;  A.  268,  27. 


98        PREPARATION  OF  ORGANIC  COMPOUNDS 

importance,  but  is  confined  to  the  production  of 
phenolic  carbinols.  When  formaldehyde  is  condensed 
with  a  phenol,  either  a  diphenyl  methane  derivative  or 
a  benzyl  alcohol  is  produced  : 

2C6H5OH  +H.CHO  =  HOC6H4.CH2.C6H4OH  +  H2O 
C6H5OH  +  H.CHO  =  HOC6H,.CH2OH 

the  entering  group  taking  the  para-  or  ortho-  position 
to  the  hydroxyl  group,  the  para-  position  being  prefer  red. 
The  former  of  the  above  reactions  takes  place  when 
the  more  powerful  condensing  agents  are  used,  but  it 
is  impossible  to  foretell  in  any  definite  case  which 
reaction  any  given  condensing  agent  will  give  rise  to. 
As  a  rule,  the  caustic  alkalis,  alkali  carbonates,  alkaline 
earth  oxides,  lead  oxide,  or  hydrochloric  acid  are  used 
to  bring  about  the  condensation.  When  hydrochloric 
acid  is  used,  the  corresponding  benzyl  chloride  is  fre- 
quently produced  ;  from  it  the  alcohol  can  be  obtained 
by  heating  with  water  or  dilute  alkalis.  Occasionally 
two  oxymethyl  groups  can  be  introduced. 

PREPARATION  OF  o.-  AND  £.-OXYBENZYL   ALCOHOLS 

(HOC6H4CH2OH) -1  Sixty  grammes  of  phenol  are  dissolved  in 
300  c.c.  of  10  per  cent,  caustic  soda,  70  grammes  of  40  per  cent. 
formaldehyde  solution  added,  and  the  whole  allowed  to 
stand  at  the  ordinary  temperature  for  several  days.  The 
solution  is  then  neutralised  with  hydrochloric  acid,  extracted 
several  times  with  ether  or  ethyl  acetate,  and  the  solvent 
then  removed  by  distillation.  If  unchanged  phenol  is  present 
in  the  residue,  it  is  removed  by  distillation  in  steam.  Finally 
the  o.-  and  ^.-oxybenzyl  alcohols  are  separated  by  fractional 
crystallisation  from  benzene.  The  ortho-  compound  being 
much  more  soluble  than  the  para-  compound,  a  fairly  complete 
separation  can  be  effected  by  shaking  the  mixture  with  cold 
benzene.  o.-Oxybenzyl  alcohol  (saligenin)  melts  at  82° ; 
^.-oxybenzyl  alcohol  at  ni°-ii20. 

PREPARATION    OF    £.-CRESOLDIMETHYLOL     (C6H2[i] 
OH[2-6](CH2OH)2[4]CH3).2     Twenty-two  grammes  of  />.-cresol 

i  B.  27,  2411  ;  D.R.P,  85,588  2  B.  40,  2524. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS        99 

are  dissolved  in  150  c.c.  of  15  per  cent,  caustic  soda  solution, 
and  30  grm.  of  40  per  cent,  formaldehyde  solution  are  added. 
After  standing  for  several  days  at  the  ordinary  temperature,  the 
solution  is  acidified  with  acetic  acid  or  saturated  with  carbon 
dioxide  and  the  precipitate  filtered  off  and  recrystallised. 
It  melts  at  133°. 

PREPARATION   OF   s-NITRO-4-OXYBENZYL    ALCOHOL 

(C6H3[i]CH2OH[3]NO2[4]OH).i  Forty  grammes  of  o.-nitro- 
phenol,  100  grm.  of  40  per  cent,  formaldehyde,  and  200  c.c. 
of  concentrated  hydrochloric  acid  are  boiled  under  a  reflux- 
condenser  for  six  hours.  After  cooling,  the  supernatant 
liquor  is  decanted  from  the  heavy  brown  oil,  and  the  latter 
distilled  in  steam  to  remove  unchanged  nitrophenol.  The 
residue  is  extracted  several  times  with  boiling  water,  and  the 
united  extracts  filtered  hot  and  then  allowed  to  cool.  Long 
yellow  needles  are  deposited,  which  after  being  recrystallised 
from  water  several  times  melt  at  97°. 

In  exactly  the  same  way  £. -nitrophenol  yields  2-oxy-5-nitro- 
benzyl  alcohol,  which  forms  colourless  needles  melting  at  128°. 

PREPARATION  OF  HEXAOXYDIPHENYL  METHANE 
DICARBOXYLIC  ACID.2  One  hundred  grammes  of  gallic  acid 
are  dissolved  in  1125  c.c.  of  hot  water,  and  375  c.c.  of  hot 
concentrated  hydrochloric  acid  and  60  grm.  of  40  per  cent. 
formaldehyde  added.  The  whole  is  heated  on  the  water-bath 
under  a  reflux  condenser  until  no  further  precipitation  takes 
place,  filtered  hot,  and  the  precipitate  well  washed  with  boiling 
water,  then  with  alcohol,  and  finally  with  ether.  The  acid  forms 
a  crystalline  powder  which  does  not  melt.  The  yield  is  57  per 
cent. 

PREPARATION  OF  s-CHLOR-4-OXYBENZYL  CHLORIDE 

(C6H3[i]CH2Cl[3]Cl[4]OH).3  Five  parts  of  o.-chlorphenol 
and  6  parts  of  40  per  cent,  formaldehyde  are  mixed,  well 
cooled  with  ice,  and  then  saturated  with  hydrochloric  acid 
gas.  The  solution  is  set  aside  for  about  two  weeks  with 
frequent  shaking,  when  an  oil  separates  out  which  soon 
becomes  crystalline.  It  is  then  pressed  on  a  porous  plate  and 
recrystallised  several  times  from  benzene,  and  from  anhydrous 

1  B.  34,  2458  ;  D.R.P.  136,680. 

2  B.  25,  946  ;    31,  260. 

3  B.  34,  2459. 


ioo      PREPARATION  OF  ORGANIC  COMPOUNDS 

petroleum  ether.  It  melts  at  93°.  The  corresponding  alcohol, 
3-chlor-4-oxybenzyl  alcohol,  is  obtained  when  the  above 
compound  is  boiled  with  water.  After  cooling,  it  is  extracted 
with  ether,  and  the  ether  removed  by  distillation.  A  clear 
yellow  oil  remains  which  becomes  crystalline  when  the  sides 
of  the  vessel  are  scratched.  It  is  recrystallised  from  benzene, 
and  forms  colourless  needles  which  melt  at  123°. 

Similar  to  the  above  reactions  is  the  condensation 
of  chlormethyl  alcohol  with  phenols,  which  sometimes 
takes  place  without  the  addition  of  a  condensing 
agent,  e.g.  chlormethyl  alcohol  and  salicylic  acid  when 
boiled  in  aqueous  solution  yield  saligenic  acid,1  or  in 
the  presence  of  hydrochloric  acid 2  or  zinc  chloride. 

(d)  Diaryl  carbinols  can  often  be  obtained  when  an 
aromatic  aldehyde  is  condensed  with  a  phenol  or  an 
aromatic  base.  Here  the  normal  course  of  the  reaction 
is  the  formation  of  a  triphenyl  methane  derivative  : 

Ar.CHO  +  2C6H5NMe2  =  ArCH(C6H4NMe2)2  +  H2O 

but  by  working  in  dilute  solutions  the  reaction  can  be 
arrested  when  only  one  molecule  of  the  phenol  or  base 
has  condensed. 

Just  as  in  the  Lederer-Manasse  synthesis,  the  para- 
position  is  preferred,  but  if  this  is  occupied  the  entering 
group  often  takes  the  ortho-  position. 

The  reaction  takes  place  in  the  presence  of  hydro- 
chloric acid.  When  an  aldehyde  is  being  condensed 
with  a  base  it  is  usually  sufficient  simply  to  employ  the 
base  in  the  form  of  its  hydrochloride. 

PREPARATION  OF  4  -  NITRO  -  4'-  DIMETHYLAMINO 
BENZHYDROL  (NO2.C6H4CHOHC6H4.NMe2).3  Fifteen 
grammes  of  ^.-nitrobenzaldehyde  and  12  grm.  of  dimethyL 
aniline  are  boiled  under  a  reflux  condenser  for  40  hours 
wrTfT  300  c.c.  of  concentrated  hydrochloric  acid.  The  solution 
is  then  diluted,  unchanged  nitrobenz aldehyde  removed  by 

1  D.R.P.  113,512. 

2  D.R.P.  113,722. 

3  D.R.P.  45,8o6. 


ALCOHOLS,  PHENOLS,  AND  MERC  APT  ANS      101 

filtration,  and  the  filtrate  neutralised.  The  benzhydrol 
separates  as  yellow  flocks  which  are  collected,  washed,  and 
freed  from  small  quantities  of  dimethyl  aniline  by  steam- 
distillation.  It  is  finally  recrystallised  from  dilute  alcohol 
and  forms  fine  yellow  needles  which  melt  at  96°.  The  yield 
is  80  per  cent. 

The  corresponding  compound  from  benzaldehyde 
and  dimethyl  aniline,  ^.-dimethylamino  benzhydrol,  is 
formed  in  the  same  way,  but  the  preparation  does  not 
go  as  smoothly  as  in  the  above  example. 

For  further  information  regarding  this  reaction  the 
reader  is  referred  to  the  original  literature.1 

(ix)  FROM  THE  HYDROCARBONS,  ETC.,  BY 
DIRECT  OXIDATION.  In  the  aliphatic  series  this  reac- 
tion can  only  take  place  if  the  hydrogen  is  attached 
to  a  tertiary  carbon  atom,  as  in  triphenyl  methane. 
The  reaction  is  of  very  minor  importance,  as  although 
the  carbinol  is  probably  the  first  product  obtained 
when  the  leuco-derivatives  of  the  triphenyl  methane 
dyes  are  oxidised,  it  is  not  isolated,  but  at  once  loses 
a  molecule  of  water  to  form  the  dyestuff,  e.g. : 

OH 

(C6H5)2CH.C6H4NMe2     -»     [(C6H6)2.C.C6H4.NMe2.HCl] 

—       (C6H5)2.C  :  C6H4  :  NMe2Cl 
Leucomalachite 
Green 

Possibly  the  free  bases  possess  the  carbinol  structure, 
but  for  further  information  on  this  subject  the  reader  is 
referred  to  works  on  tinctorial  chemistry.  See  also 
pp.  288-297. 

PREPARATION    OF    TRIPHENYL    CARBINOL 

(C6H5)3C.OH.2  Twelve  grammes  of  triphenyl  methane  are 
dissolved  in  60  grm.  of  glacial  acetic  acid  and  the  solution 
warmed  on  the  water-bath.  Twelve  grammes  of  chromic  acid 
are  slowly  added,  and  the  warming  continued  until  a  sample 

1  B.  21,  3292  ;  42,  4163  ;    D.R.P.  45,8o6,  119,461. 

2  B.  14,  1944. 


102      PREPARATION  OF  ORGANIC  COMPOUNDS 


poured  into  water  gives  a  precipitate  which  does  not  melt  when 
the  water  is  boiled  (about  i  to  i^  hours).  The  whole  is  then 
poured  into  water,  and  the  precipitate  recrystallised  from 
benzene.  M.P.  159°.  Yield  80  to  90  per  cent. 

The  hydrogen  atoms  in  aromatic  compounds  can 
occasionally  be  oxidised  to  hydroxyl  by  the  action  of 
hydrogen  peroxide  in  glacial  acetic  acid.1  In  the 
case  of  anthraquinone,  oxidation  takes  place  more 
readily,  and  the  technical  preparation  of  alizarine 
consists  in  heating  the  /3-sulphonic  acid  with  caustic 
soda  and  potassium  chlorate  in  closed  vessels  : 


CO 


CO 


S03Na 


CO    OH 
/\/V\QH 


CO 

Alizarine 


Anthraquinone  can  also  be  oxidised  to  oxyanthra- 
quinones  by  heating  with  oleum  or  nitrosyl  sulphuric 
acid  in  the  presence  of  boric  acid,  the  boric  acid  forming 
boric  esters  and  hence  allowing  the  oxidation  to  be 
carried  out  at  a  higher  temperature  than  would  be 
otherwise  possible.2 

(x)  FROM  THE  QUINONES  BY  THE  ADDITION 
OF  PHENOLS.  The  true  quinones,  such  as  benzo- 
quinone,  readily  add  on  two  molecules  of  a  phenol  to 
form  an  addition  compound,  e.g.  : 


HO 


O  :  C6H4  :  O  +  2C6H5OH    = 


H0/ 


/OH 

4<^ 

XOC6H5 
Phenoquinone 


With  hydroquinones  only  one  molecule  is  taken  up, 
a  quinhydrone  being  formed  : 

1  Soc.  97,  1659. 

2  D.R.P.  65,375,68,114,  68,123,  64,418,  81,481,  &c. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS      103 

O—  C6H4—  O 
O  :  C6H4  :  O  +  C6H4(OH)2  =        ^>C6H4<^ 

HO  OH 

The  reaction  takes  place  very  readily,  the  highly 
coloured  addition  products  being  produced  when  the 
solutions  of  the  two  components  are  mixed.  Hence 
the  quinhydrones  are  the  first  products  formed  when  the 
quinones  are  prepared  by  oxidising  the  hydroquinones, 
or  when  the  quinones  are  reduced  to  the  hydro- 
quinones, and  by  using  only  half  the  quantity  of  the 
reducing  or  oxidising  agent  demanded  by  the  equation  : 

C6H4(OH)2      ^      0:C6H4:0 
H2 

they  may  be  readily  isolated. 

PREPARATION  OF  PHENOQUINONE,1 
C6H50X  xOC6H5 

^CeH^  .  1    One     part    of     benzoquinone     and 

H(X  XOH 

2  parts  of  phenol  are  heated  under  a  reflux  condenser  in 
ligroin  solution  for  a  few  minutes.  On  cooling  (the  solution 
having  been  concentrated  if  necessary),  the  phenoquinone 
separates  out  as  red  needles  with  a  green  reflex.  M.P.  71°. 
Resorcin-quinone  is  best  prepared  in  benzene  solution.  Almost 
black  needles  with  green  reflex.  Decomposes  at  about 
90°.  Pyrogallol-quinone  (purpurogallein)  is  similar. 


PREPARATION   OF    QUINHYDRONE,2      O 


/64v 
/ 


This  compound  can  be  obtained  by  warming  quinone  and 
hydroquinone  in  aqueous  solution,  but  is  most  readily  pre- 
pared by  warming  hydroquinone  in  aqueous  solution  with 
half  the  quantity  of  ferric  chloride  necessary  for  its  oxidation 
to  quinone.  It  forms  green  prisms  with  a  strong  metallic 
lustre.  M.P.  171°. 

1  A.  200,  251  ;  215,  134.  2  B.  24,  1341- 


io4      PREPARATION  OF  ORGANIC  COMPOUNDS 

(xi)  FROM  THE  a-DIKETONES  BY  INTRA- 
MOLECULAR REARRANGEMENT.  This  rearrange- 
ment of  the  aromatic  a-diketones  into  derivatives  of 
glycollic  acid  under  the  action  of  caustic  alkalis  is 
discussed  on  p.  172.  It  may  be  pointed  out  that 
phenanthraquinone  undergoes  a  similar  rearrange- 
ment : 

'\  /\ 


COOH 


\/ 

Phenanthraquinone  Diphenylene  glycollic  acid 

THE  MERCAPTANS 

The  mercaptans,  or  thioalcohols,  form  a  rather 
unimportant  class  of  compounds,  and,  on  account  of 
their  disgusting  odour,  are  unpleasant  to  deal  with. 

The  aliphatic  members  are  usually  best  obtained 
by  distilling  the  sodium  salts  of  alkyl  sulphuric  acids 
with  sodium  sulphydrate  in  aqueous  solution.1  The 
corresponding  sulphide  is  formed  simultaneously,  but 
the  mercaptan  is  readily  separated  by  washing  with 
caustic  potash  solution,  in  which  it  dissolves  to  form 
a  mercaptide,  and  then  decomposing  the  alkaline  solu- 
tion with  mineral  acids. 

The  mercaptans  can  also  be  obtained  by  reducing 
the  sulphochlorides  with  zinc  and  sulphuric  acid,  or 
from  the  halogen  compounds  by  double  decomposition 
with  sodium  sulphydrate  or  sodium  disulphide,  the 
disulphide  formed  in  the  latter  case  being  subse- 
quently reduced  with  zinc  and  hydrochloric  acid. 

*  B.  20,  3409. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS      105 

PREPARATION  OF  THIOGLYCOLLIC  ACID  (HS.CH?. 
COOH).  (a)1  One  hundred  grammes  of  chloracetic  acid 
are  dissolved  in  500  c.c.  of  water  and  accurately  neutralised 
with  potassium  carbonate  or  caustic  potash.  To  the  cold 
solution  500  c.c.  of  aqueous  potassium  sulphydrate,  containing 
80  grm.  KSH,  are  added  slowly  with  continual  agitation,  and 
the  whole  then  heated  for  fifteen  minutes  on  the  water-bath. 
A  concentrated  aqueous  solution  of  250  grm.  of  crystallised 
barium  chloride  and  100  c.c.  of  25  per  cent,  ammonia  are  added, 
and  the  whole  then  set  aside.  After  standing  several  hours 
crystallisation  can  be  induced  by  violently  shaking  the  liquid 
and  scratching  the  sides  of  the  vessel.  The  barium  salt  is 
filtered  off  and  forms  shining  monosymmetric  tablets  having 
the  formula  : 

S— CH2— CO 
\       /     +3H20 
BaO 

In  order  to  obtain  the  free  acid,  the  barium  salt  is  ground 
up  with  3  parts  of  12  per  cent,  hydrochloric  acid,  extracted 
several  times  with  ether,  the  ethereal  extract  dried,  and  the 
ether  then  removed  by  distillation  from  the  water-bath.  The 
residue  is  finally  fractionated  in  vacuo,  when  the  free  acid 
passes  over  as  a  colourless  oil  boiling  at  iO7°-io8°  at  16  mm. 

(b)  2  Chloracetic  acid  (9*45  grm.)  is  dissolved  in  40  c.c.  of  water 
and  neutralised  with  5-5  grm.  of  sodium  carbonate.  A  cold 
solution  of  sodium  disulphide,  obtained  by  boiling  12 '8  grm. 
crystallised  sodium  sulphide  with  3-2  grm.  of  sulphur  and  35  c.c. 
of  water,  is  then  slowly  added,  the  temperature  being  allowed 
to  rise  to  about  40°.  The  whole  is  digested  for  one  hour  at 
95°,  cooled,  filtered,  and  the  filtrate  treated  at  70°  with  7-7  grm. 
zinc  dust  and  41  grm.  concentrated  hydrochloric  acid.  After 
filtering,  the  liquid  is  neutralised  with  sodium  carbonate,  and 
the  sodium  salt  salted  out  with  sodium  chloride,  or  it  is  made 
alkaline  with  ammonia,  barium  chloride  (25  grm.)  added,  and 
the  barium  salt  treated  as  in  the  first  preparation. 

Thioglycollic  acid  is  of  increasing  importance  for  the 
manufacture  of  the  thioindigoid  vat-dyes. 

Even  halogen  atoms  attached  to  a  benzene  nucleus 3 

1  B.  39,  733.  2  D.R.P.  180,875. 

3  When  nitro-groups  are  present  in  the  ortho-  or  para-  position, 
the  halogen  atom  is  much  more  readily  replaced.  Cf.  p.  152. 


io6      PREPARATION  OF  ORGANIC  COMPOUNDS 

can  sometimes  be  replaced  by  the  mercaptan  group, 
but  in  this  case  a  contact  substance,  such  as  a  copper 
salt,  must  be  added. 

PREPARATION     OF     TH  IOS  ALIC  YLIC    ACID 

1    Fifty  grammes  of  o.-chlorbenzoic  acid  are 


mixed  with  a  little  water  and  then  38-5  grm.  of  caustic  soda 
of  40°  Be.  (13-5  grm.  NaOH  in  25  c.c.  water),  100  grm.  of 
sodium  sulphydrate,  and  0-5  grm.  of  crystallised  copper  sulphate 
carefully  mixed  in.  The  whole  is  then  heated  with  continual 
stirring  to  i5o°-2OO°.  The  mass  soon  becomes  dark  red  and 
melts.  The  temperature  is  then  raised  to  250°,  when  the  mass 
becomes  thick,  heats  spontaneously,  and  gradually  solidifies. 
The  cooled  melt  is  dissolved  in  a  litre  of  water  and  the  thio- 
salicylic  acid  precipitated  from  the  filtered  solution  with 
hydrochloric  acid.  The  yield  is  almost  quantitative. 

Thiosalicylic  acid  is  also  of  importance  as  an  inter- 
mediate product  in  the  manufacture  of  thioindigoid 
dyes. 

Another  important  method  for  producing  aromatic 
mercaptans  is  by  the  replacement  of  the  diazo-group. 
This  replacement  can  be  brought  about  in  several 
ways,  viz.  : 

(i)  The  diazo-chloride  is  treated  with  potassium 
xanthate,  and  the  xanthic  ester  then  hydrolysed  :  2 


Ar.N:N.Cl  +  KS.C^  =  ArS.C<  +  KC1  +  N2 

XOEt  \OEt 

+  5H2O  =  ArSH  +  EtOH  +  H2S  +  CO2 
\OEt 

(ii)  The  diazo-salt  is  treated  with  potassium  and 
copper  thiocyanates  and  the  aryl  thiocyanate  thus 
formed  hydrolysed.3 

(iii)  The  diazo-solution  is    treated  with  potassium 
sulphydrate,  when  the  mercaptan  is  formed  directly.4 
i  D.R.P.  189,200.  2  J.  pr.  [2]  41,  184. 

3  B.  23,  738,  770.  4  B.  20,  349. 


ALCOHOLS,  PHENOLS,  AND  MERCAPTANS      107 

(iv)  The  diazo-solution  is  treated  with  sodium  poly- 
sulphide  and  the  polysulphide  then  reduced.1 

PREPARATION    OF    TH  I  OS  ALI  CYLIC    ACID 

2     Ten  parts  of    anthranilic    acid    are    dis- 


solved  in  1  50  to  200  parts  of  dilute  hydrochloric  acid  containing 
5  parts  of  HC1,  ice  (20  parts)  is  added,  and  the  whole  diazotised 
in  the  usual  way  with  6-7  parts  of  sodium  nitrite.  Sulphuretted 
hydrogen  is  then  passed  into  the  diazo-solution  until  the  yellow 
precipitate  which  at  first  separates  becomes  bright  red.  This 
is  due  to  the  formation  of 

N  :  N.SH 
—  COOH 

The  still  moist  precipitate  is  dissolved  in  sodium  carbonate 
solution,  and  the  whole  warmed  until  a  sample  gives  a  pure 
white  precipitate  with  hydrochloric  acid.  The  solution  is 
then  made  acid  (Congo  paper)  with  hydrochloric  acid,  and  the 
precipitated  thiosalicylic  acid  filtered  off  and  washed  with  cold 
water. 

1  Pat   Anm.  Kl.  12.  q.  30,607,  32,070. 

2  D.R.P.  69,073. 


CHAPTER  V 

ALDEHYDES,  KETONES,  QUINONES  (AND 
QUINONE-IMIDES),  AND  SOME  DERIVA- 
TIVES OF  THE  SAME 

A.  THE  ALDEHYDES 

BEFORE  discussing  the  various  methods  of  preparing 
the  aldehydes,  a  few  words  must  be  said  on  the  methods 
employed  for  isolating  and  purifying  the  same.  For 
this  purpose  it  is  usual  to  convert  the  aldehyde  into 
a  derivative  which  crystallises  well,  and  which  can  be 
readily  decomposed  into  the  original  aldehyde.  Such 
derivatives  are  numerous,  and  some  of  the  most 
important  will  be  found  discussed  at  the  end  of  this 
chapter. 

Ammonia  is  occasionally  used  (see  p.  109)  and  the 
resulting  aldehyde-ammonia  decomposed  by  distilling 
with  acids  : 

XH 

2R.C-OH   +  H2S04  -  2R.CHO  +  (NH4)2SO4. 


More  commonly  the  crude  aldehyde  is  shaken  up  with  a 
concentrated  solution  of  sodium  bisulphite,  and  the 
resulting  bisulphite  compound  decomposed  by  distilling 
with  sodium  carbonate  solution  : 

+Na2C03«=2R.CHO  +2Na2SO3  +CO2  +H2O. 


This  method  is  fairly  general,  but  is  inapplicable  in 
some  cases,  especially  in  the  terpene  series,  where  the 
aldehyde  is  very  sensitive  to  acids.  In  such  cases 
the  aldehyde  can  be  combined  with  an  amino-carboxylic 

108 


ALDEHYDES,    KETONES,   QUINONES  109 

or  amino-sulphonic  acid,  the  resulting  compound  being 
usually  decomposed  by  steam  distillation,  without  the 
addition  of  acids  : 

R.CH  :NR'SO3Na  +H2O  -R.CHO  +  NH2R'SO3Na. 

The  most  usual  amino-sulphonic  acid  to  use  is  naph- 
thionic  acid  (a-naphthylamine-4-sulphonic  acid)  either 
in  the  form  of  its  sodium  or  its  barium  salt.  The  latter 
salt  has  the  advantage  of  giving  condensation  products 
which  are  practically  insoluble.  Sugars  are  best 
isolated  as  their  phenylhydrazones,  e.g.  : 

CH2OH(CHOH)4.CH  rN.NHPh. 

I.  OXIDATION  OF  PRIMARY  ALCOHOLS.  This 
method  is  most  frequently  employed  in  the  aliphatic 
series,  especially  for  oxidising  polyhydric  alcohols  to 
the  corresponding  polyoxyaldehydes  (the  aldoses). 
For  the  oxidation  of  monohydric  alcohols,  potassium 
bichromate  and  sulphuric  acid  are  usually  employed, 
but  the  oxidation  can  often  be  brought  about  by 
atmospheric  oxygen  in  the  presence  of  contact  sub- 
stances. Thus  formaldehyde  is  prepared  technically  by 
passing  methyl  alcohol  vapour  and  air  over  copperised 
asbestos,  the  heat  of  the  reaction  being  sufficient  to 
keep  the  asbestos  at  a  dull  red  heat. 

PREPARATION  OF  ACET ALDEHYDE  (CH3CHO).  Two 
hundred  cubic  centimetres  of  water  and  60  c.c.  of  concentrated 
sulphuric  acid  are  placed  in  a  flask  fitted  with  a  condenser  * 
and  tap-funnel,  and  heated  to  boiling.  The  flame  is  then 
removed  and  a  solution  of  200  grm.  of  sodium  dichromate  in 
200  c.c.  of  water  and  125  c.c.  of  alcohol  slowly  added  through 
the  tap-funnel.  Considerable  heat  is  given  out,  and  the 
bichromate  solution  should  be  added  at  such  a  rate  as  to 
keep  the  whole  boiling  fairly  briskly.  The  distillate,  which 
consists  chiefly  of  aldehyde,  alcohol,  and  water,  is  then  distilled 
from  the  water -bath  through  a  sloping  reflux  condenser  (Fig. 
50)  into  100  c.c.  of  dry  ether,  which  is  kept  cold  by  means 

1  The  water  in  the  condenser  should  be  as  cold  as  possible 
andrthe  receiver  should  be  cooled  with  ice. 


no   PREPARATION  OF  ORGANIC  COMPOUNDS 

of  ice  or  a  freezing  mixture.  The  water  in  the  condenser 
should  be  maintained  at  a  temperature  of  3o°-35°  in  order 
to  condense  the  alcohol  and  water,  but  not  the  aldehyde. 
The  bulb  A  is  to  prevent  the  ether  being  sucked  back.  The 
aldehyde  dissolves  in  the  ether,  and  the  solution  thus  obtained 
is  saturated  with  dry  ammonia  gas  (see  p.  31)  and  then 
allowed  to  stand  for  an  hour.  The  colourless  crystals  of  alde- 
hyde ammonia,  CH3.CH  (OH)  (NH2),  which  separate  are 
collected,  washed  with  ether,  and  dried  between  filter-paper 


FIG.  50. 

at  the  ordinary  temperature.  Yield  about  30  grm.  The 
compound  is  dissolved  in  its  own  weight  of  water,  3^-  parts  of 
cold,  40  per  cent,  sulphuric  acid  added,  and  the  whole  distilled 
from  the  water -bath.  As  aldehyde  boils  at  21°,  ice-water 
should  be  run  through  the  condenser,  and  the  receiver  should 
be  cooled  in  a  freezing  mixture.  The  distillate  is  dried  with 
calcium  chloride  and  redistilled  from  a  water-bath  heated  to 
30°.  It  forms  a  colourless  liquid  with  a  pleasant  smell. 

Alcohol  can  also  be  oxidised  by  treating  it  with  a 
stream  of  chlorine  gas.  Simultaneous  chlorination  takes 
place,  trichloracetaldehyde  (chloral),  CC13CHO,  being 


ALDEHYDES,  KETONES,  QUINONES      in 

formed.  This  unites  with  excess  of  alcohol  to  form 
the  alcoholate,  CC13CH(OH)(OC2H5).  The  reaction 
commences  in  the  cold  and  is  completed  by  raising  the 
temperature  to  the  boiling-point. 

The  oxidation  of  polyhydric  alcohols  to  aldoses  is 
best  brought  about  by  dilute  nitric  acid,  sodium 
carbonate  and  bromine,  or  hydrogen  peroxide  in  the 
presence  of  traces  of  ferrous  sulphate  (Fenton's  reagent) . 
The  sugars,  which  are  troublesome  to  obtain  in  the  free 
state,  are  isolated  as  their  phenylhydrazones. 

PREPARATION     OF     MANNOSE    PHENYLHYDRAZONE 

(CH2OH  (CHOH)4CH  :  N .  NHPh)  .1  Sixty  grammes  of  mannite 
are  added  to  400  c.c.  of  water  and  200  c.c.  of  concentrated 
nitric  acid  (D  =  1-41),  and  the  whole  heated  to  a  temperature 
of  40°  to  45°.  After  two  or  three  hours  red  fumes  appear, 
and  the  liquid  must  then  be  tested  every  twenty  minutes  by 
withdrawing  a  small  sample,  neutralising  with  crystallised 
sodium  carbonate,  and  then  adding  a  little  phenyl  hydrazine 
dissolved  in  acetic  acid,  care  being  taken  that  the  whole  shows 
an  acid  reaction.  When  a  sample  so  treated  deposits  a 
heavy  yellow  precipitate  on  standing  for  a  few  minutes,  the 
heating  is  stopped  and  the  reaction  mixture  cooled  as  rapidly 
as  possible.  It  is  rendered  alkaline  by  the  addition  of  crystal- 
lised sodium  carbonate,  the  carbon  dioxide  evolved  sweep- 
ing the  liquid  clear  of  nitrous  acid.  It  is  then  acidified 
with  acetic  acid,  and  20  grm.  of  phenyl  hydrazine  dissolved 
in  dilute  acetic  acid  added.  On  standing  over-night  the 
hydrazone  is  deposited  as  pale  yellow  needles.  M.P.  195°. 
Yield  6  grm.  The  testing  every  twenty  minutes  is  very 
necessary,  as  if  the  oxidation  is  carried  too  far  the  aldehyde  will 
be  oxidised  to  the  corresponding  carboxylic  acid.  The  sugar 
itself  can  be  obtained  by  boiling  the  hydrazone  with  concen- 
trated hydrochloric  acid,  but  it  is  very  troublesome  to  isolate. 
The  oxidation  can  also  be  carried  out  as  follows.2  Twenty 
grammes  of  mannitol  are  dissolved  in  100  c.c.  of  water  contain- 
ing 5  grm.  of  crystallised  ferrous  sulphate.  The  solution  is 
well  cooled  and  then  60  c.c.  of  20  volume  (6  per  cent.}  hydrogen 
dioxide  slowly  run  in.  The  whole  is  made  just  alkaline 
with  sodium  carbonate,  acidified  with  acetic  acid,  and  then 
treated  with  6  grm.  of  phenyl  hydrazine  dissolved  in  dilute 

i  B.  22,  365.  2  Soc.  75,  9. 


ii2      PREPARATION  OF  ORGANIC  COMPOUNDS 

acetic  acid.  After  standing,  the  hydrazoneis  collected,  washed, 
ground  up  with  acetone,  and  recrystallised,  first  from  boiling 
water,  then  from  60  per  cent,  alcohol,  and  finally  twice  from 
water  containing  animal  charcoal. 

II.  OXIDATION  OF  AROMATIC  HYDRO- 
CARBONS. For  the  direct  oxidation  of  aromatic  hydro- 
carbons to  aldehydes  a  variety  of  oxidising  agents  is 
available. 

(a)  Chromyl  chloride  (Etard's  reaction) .     The  hydro- 
carbon is  dissolved  in  10  parts  of  carbon  bisulphide, 
and  the  chromyl  chloride  dissolved  in  the  same  solvent 
slowly  added  with  continual  cooling.     A  brown  com- 
pound, RCH(OCrCl2OH)2,  is  precipitated  and  is  finally 
decomposed  with  water.    This  method  is  not  often 
used  as  the  reaction  is  often  dangerously  violent  and 
the  intermediate  compounds  are  very  explosive. 

(b)  Chromic  acid.      As   chromic  acid    oxidises    the 
aldehydes  to  carboxylic  acids,  the  aldehyde  must  be 
protected  at  the  moment  of  its  formation.     To  bring 
about  this  result  the  oxidation  is  carried  out  in  acetic 
anhydride    solution  in  the  presence  of   concentrated 
sulphuric  acid.     Under  these  conditions  the  aldehyde 
is  at  once  converted  into  its  diacetate,  and  as  this  is 
not  attacked  by  chromic  acid  it  can  be  isolated  and 
subsequently  hydrolysed  by  boiling  with  acids 

R.CHO  +  (CH3CO)20  =  RCH(OCOCH3)s 
R.CH(OCOCH3)2 '+  H20  =  RCHO  +  2CH3COOH. 

PREPARATION  OF  ISO-PHTHALALDEHYDE,  C6H4 
(CHO)2[i'3].1  Twenty-five  grammes  of  w.-xylene  are  dis- 
solved in  a  mixture  of  1000  grm.  of  acetic  anhydride,  400  grm. 
of  glacial  acetic  acid,  and  15  grm.  of  concentrated  sulphuric 
acid.  One  hundred  grammes  of  chromic  acid  are  then  slowly 
added,  the  temperature  being  kept  at  about  5°.  When  all 
the  chromic  acid  has  been  added,  the  whole  is  allowed  to  stand 
at  the  above  temperature  until  a  sample  gives  a  copious  white 
precipitate  when  shaken  with  cold  water  until  the  acetic 
anhydride  is  destroyed.  The  whole  is  then  poured  on  to  excess 

i  D.R.P.  121,788  ;  A.  311,  353. 


ALDEHYDES,   KETONES,   QUINONES  113 

of  ice  and  stirred  mechanically  until  the  oily  substance  at  first 
precipitated  becomes  solid.  The  ^so-phthalaldehyde  tetrace- 
tate  is  then  collected  and  recrystallised  from  methyl  alcohol. 
It  forms  colourless  prisms  melting  at  101°. 

To  obtain  the  free  aldehyde,  the  tetracetate  is  boiled  for 
a  short  time  with  4  parts  of  5  per  cent,  hydrochloric  acid.  On 
cooling,  the  aldehyde  separates  out  in  long  needles  melting  at 
89°.  It  may  be  purified  by  recrystallisation  from  water. 

(c)  Cerium  dioxide.  The  oxidation  is  carried  out  in 
the  presence  of  fairly  strong  sulphuric  acid  : 

Ce02  +  H2S04  =  CeS04  +  H2O  +  O. 

Technical  cerium  dioxide  is  usually  a  brown  powder 
containing  60  to  70  per  cent,  of  CeO2.  The  amount  of 
active  oxygen  is  readily  estimated  by  treating  with 
hydrochloric  acid  and  potassium  iodide  and  then 
titrating  the  liberated  iodine  in  the  usual  way. 

PREPARATION  OF  BENZ ALDEHYDE  (C6H5CHO).i  One 
litre  of  60  per  cent,  sulphuric  acid  and  30  grm.  of  toluene  are 
heated  to  60°  in  a  flask  provided  with  a  reflux  condenser 
and  mechanical  stirrer.  Two  hundred  grammes  of  technical 
cerium  dioxide  are  then  gradually  added,  and  the  tempera- 
ture allowed  to  rise  to  90°.  When  the  brown  dioxide  has 
changed  to  the  white  sulphate  the  whole  is  steam-distilled, 
a  mixture  of  unchanged  toluene  and  benzaldehyde  passing 
over.  These  may  be  separated  by  fractional  distillation,  but 
it  is  better  to  shake  the  whole  on  a  shaking-machine  for  some 
hours  with  concentrated  sodium  bisulphite  solution.  If  any 
crystals  separate,  water  is  added  until  they  dissolve.  The 
aqueous  layer  is  then  removed  and  solid  sodium  carbonate 
added  until  an  alkaline  reaction  is  obtained.  The  whole  is 
again  steam-distilled,  the  benzaldehyde  separated  by  means 
of  a  tap-funnel,  dehydrated  over  calcium  chloride,  and  finally 
distilled  in  a  current  of  hydrogen.  It  forms  a  colourless  oil 
with  a  pleasant  smell.  B.P.  179°. 

On  the  manufacturing  scale  the  following  oxidising 
agents  have  met  with  great  success,  but  for  further 
details  the  reader  is  referred  to  the  literature :  (a) 

i  D.R.P.  158,609. 


n4   PREPARATION  OF  ORGANIC  COMPOUNDS 

manganese  dioxide  and  sulphuric  acid,  D.R.P.  101,221  ; 
(b)  ammonium  manganese  alum,  Mn2(SO4)3.(NH4)2SO4, 
prepared  by  the  electrolysis  of  ammonium  manganese 
sulphate  and  sulphuric  acid,  D.R.P.  189,178;  (c)  man- 
ganese persulphate,  Mn(SO4)2,  prepared  by  the  elec- 
trolysis of  manganous  sulphate  and  sulphuric  acid, 
D.R.P.  163,813;  (d)  ozone.  This  last  reagent  is  used 
for  preparing  aldehydes  by  the  rupture  of  a  double 
bond.  Ozonides  (highly  explosive  bodies)  are  formed 
as  intermediate  compounds,  and  then  undergo  decom- 
position into  two  molecules  of  aldehyde  or  one  molecule 
of  aldehyde  and  one  of  ketone  : 


HR.CH  :  CR2  +  03  =R.CH  -  CR2  = 
RCHO  +  R2CO  +  O. 

For  the  preparation  of  vanillin  from  isoeugenol  by 
this  method,  see  D.R.P.  97,620  : 

CH:CH.CH3        CHO 


OCH, 


OCH, 


L3 

OH  OH 

Isoeugenol  Vanillin 

What  is  probably  a  modification  of  this  method 
consists  in  blowing  fine  streams  of  air  through  isoeugenol 
which  is  simultaneously  submitted  to  the  action  of 
ultra-violet  light.  The  yield  is  said  to  be  about  95  per 
cent.  D.R.P.  224,071. 

For  the  indirect  oxidation  of  side-chains  three  methods 
are  available,  viz.  : 

(i)  The  di-halogen  compound  is  prepared  and  then 
boiled  with  water,  sodium  carbonate  solution,  or 
chalk  : 

R.CHC12->(RCH(OH)2)->R.CHO  +  H2O. 

PREPARATION  OF  BENZALDEHYDE  (PhCHO).  Fifty 
grammes  of  benzalchloride,  C6H6CHC12,  are  heated  under  a 


ALDEHYDES,  KETONES,  QUINONES  115 

reflux  condenser  on  the  oil-bath  (temperature  of  bath,  130°) 
with  250  c.c.  of  water  and  80  grm.  of  precipitated  calcium 
carbonate.  At  the  end  of  four  hours  the  whole  is  steam-dis- 
tilled. The  distillate  is  worked  up  as  described  on  p.  113. 

(ii)  The  mono-halogen  compound  is  condensed  with 
a  primary  aromatic  amine  (e.g.  aniline  or,  better, 
sulphanilic  acid) ,  and  the  benzylaniline  derivative  thus 
obtained  oxidised  to  the  corresponding  benzylidene  com- 
pound. This  latter  is  then  split  by  heating  with 
hydrochloric  acid  : 

ArCH2Cl  +  HNHC6H5  =  ArCH2.NHC6H5  +  HC1 

ArCH2NHC6H5  +  O  =  ArCH  :  NC6H5  +  H2O 

ArCH  :  N.C6H5  +  H2O  =  ArCHO  +  C6H6NH2 

PREPARATION       OF       o.-NITROBENZALDEHYDE 

(C6H4[i]NO2[2]CHO).1  Twenty-three  grammes  of  o.-nitro- 
benzylaniline  are  dissolved  in  acetone,  and  the  solution  cooled 
to  10°.  A  cold  saturated  solution  of  12-5  grm.  potassium 
permanganate  is  then  slowly  added,  the  whole  being  con- 
tinually and  vigorously  stirred.  The  solution  is  then  filtered 
and  the  acetone  removed  by  distillation.  The  resulting 
o.-nitrobenzylidene  aniline  is  hydrolysed  by  mixing  with  15 
parts  of  cold,  concentrated  hydrochloric  acid.  The  aldehyde 
crystallises  out  and  can  be  further  purified  by  steam-distilla- 
tion and  recrystallisation  from  water.  Long,  pale-yellow 
needles.  M.P.  46°. 

(iii)  In  some  cases  where  negative  groups,  such  as 
nitro-groups,  are  present  in  the  0.-  and  p.-  positions  to 
the  side-chain,  the  hydrogen  of  the  latter  is  rendered 
sufficiently  active  to  condense  with  ^>.-nitroso-di- 
methylaniline.  The  anil,  ArCH  :  NC6H4NMe2,  is  then 
split  by  treatment  with  acids. 

PREPARATION        OF         2.4-DINITROBENZALDEHYDE 

(C6H3 [i  ]CHO [2 .4]  (NO2)2)  .*  Forty-five  grammes  of  2.4-dinitro- 
toluene,  40  grm.  of  £.-nitroso-dimethylaniline,  and  75  grm.  of 

1  D.R.P.  91,503,  92,684. 
B.  35,  1228  ;  D.R.P.  121,745. 


n6      PREPARATION  OF  ORGANIC  COMPOUNDS 

crystallised  sodium  carbonate  are  heated  under  a  reflux 
condenser  on  the  water-bath  for  five  hours  with  250  c.c.  of 
alcohol.  The  anil  separates  out  in  dark  green  granules, 
which  are  collected  and  washed  with  several  litres  of  boiling 
water.  Yield  86  per  cent.  (67  grm.).  A  sample  may  be 
purified  by  recrystallisation  from  a  little  acetone.  The  whole 
is  then  shaken  for  some  hours  with  250  c.c.  of  27  per  cent. 
nitric  acid  and  250  c.c.  of  benzene.  The  very  dark-coloured 
liquid  thus  obtained  is  filtered,  and  then  readily  separates  into 
two  layers.  The  benzene  layer  is  removed  and  the  benzene 
distilled  off.  An  oil  is  left  which  solidifies  on  cooling.  It  is 
dissolved  in  alcohol,  boiled  with  animal  charcoal,  filtered,  and 
water  added  to  the  filtrate  until  a  slight  cloudiness  appears. 
The  whole  is  then  set  aside  at  the  ordinary  temperature  in 
an  evaporating  basin,  when  long  yellow  needles  gradually 
separate.  These  contain  one  molecule  of  alcohol  of  crystallisa- 
tion, which  is  lost  on  heating  to  90°.  Dinitrobenzaldehyde 
melts  at  72°.  Another  6  grm.  can  be  obtained  from  the  aqueous 
layer  by  again  shaking  up  with  benzene  and  nitric  acid,  thus 
making  the  total  yield  88  per  cent. 

III.  REDUCTION  OF  THE  ACIDS.  The  reduction 
may  be  brought  about  by  distilling  the  barium  or 
calcium  salt  of  the  acid  with  barium  or  calcium  for- 
mate, but  this  method  is  not  much  used.  The  phenol 
carboxylic  acids  of  the  benzene  series  are  readily 
reduced  by  the  action  of  sodium  amalgam  and  boric 
acid,  and  as  the  yields  are  good,  this  often  forms  a 
convenient  means  of  obtaining  the  phenolic  aldehydes. 

PREPARATION  OF  SALICYLALDEHYDE  (C6H4[i] 
OH^jCHO).1  Fifteen  grammes  of  salicylic  acid  are  dissolved 
in  hot  water  and  accurately  neutralised  with  sodium  carbonate. 
The  solution  is  then  diluted  to  I  litre,  heated  to  boiling, 
1 8  grm.  of  ^.-toluidine  added,  and  the  whole  then  allowed 
to  cool  with  continual  stirring.  Two  hundred  and  fifty 
grammes  of  common  salt  and  15  grm.  of  boric  acid  are  added, 
and  then  gradually  and  with  continual  stirring,  340  grm.  of 
2  per  cent,  sodium  amalgam.  During  the  addition  of  the 
amalgam  the  solution  must  be  kept  faintly  acid  by  the  addition 
of  more  boric  acid  from  time  to  time  (about  120  grm.  will  be 
required).  The  reduction  is  complete  when  a  filtered  sample 

i  B.  41,  4147. 


ALDEHYDES,   KETONES,   QUINONES  117 

gives  no  precipitate  of  salicylic  acid  on  the  addition  of  hydro- 
chloric acid.  The  condensation  product  with  the  toluidine 
(C6H4CH3N  :  CHC6H4OH)  is  then  removed  by  nitration, 
mixed  with  dilute  sulphuric  acid,  and  steam-distilled.  The 
aldehyde  passes  over  and  is  extracted  from  the  distillate  with 
ether.  The  ethereal  solution  is  dried  with  calcium  chloride, 
and  the  ether  distilled  off.  The  residual  aldehyde  is  finally 
purified  by  distillation.  Colourless  pleasant-smelling  oil 
boiling  at  196°.  Yield  7-5  grm. 

An  electrical  modification  of  this  method  has  been 
described.  D.R.P.  196,239. 

For  the  electrolytic  reduction  of  oxalic  acid  to 
glyoxylic  acid,  see  B.  37,  3188. 

IV.  THE  ALDOL  CONDENSATION.  This  conden- 
sation allows  of  the  building  up  of  the  higher  aldehydes 
from  the  lower  members.  The  condensation  takes 
place  between  the  aldehydic  group  of  one  molecule 
and  the  a-hydrogen  atom  of  another  molecule  : 

2R.CH2.CHO  =  R.CH2.CHOH.HCR.CHO 

and,  hence,  is  limited  to  aldehydes  containing  at  least 
one  a-hydrogen  atom.  The  reaction  can  also  take 
place  between  two  different  aldehydes,  and  in  this  case 
only  one  of  them  need  contain  an  a-hydrogen  atom  : 

R.CH2.CHO  +  R'.CHO  =  R'.CHOH.HCR.CHO. 

In  both  cases  the  condensation  is  usually  accom- 
panied by  a  simultaneous  loss  of  water,  the  unsaturated 
aldehyde  being  the  result  : 

CH3CHOH.CH2.CHO  =  CH3.CH  ICH.CHO. 

The  condensation  is  brought  about  by  a  variety 
of  reagents,  such  as  hydrochloric  acid,  sodium  acetate, 
sodium  carbonate,  sodium  sulphite,  and  potassium 
cyanide.  This  last  has  the  special  advantage  of  not 
causing  the  loss  of  water. 

PREPARATION  OF  ALDOL  (CH3.CHOH.CH2.CHO).i 
One  hundred  grammes  of  freshly  prepared  acetaldehyde  are 
slowly  added  to  200  c.c.  of  ice-water,  care  being  taken  that  the 

1  A.  306,  323. 


n8   PREPARATION  OF  ORGANIC  COMPOUNDS 


temperature  of  the  mixture  does  not  exceed  o°.  The  solution 
thus  obtained  is  cooled  to  -  12°,  and  then  100  c.c.  of  an  ice-cold, 
•2\  per  cent,  solution  of  potassium  cyanide  slowly  added.  During 
the  addition  of  the  cyanide  the  whole  must  be  well  stirred 
and  care  must  be  taken  to  keep  the  temperature  below  -  8°. 
When  all  the  cyanide  has  been  added  the  whole  is  allowed  to 
stand  for  two  hours  in  a  freezing  mixture,  and  then  for  thirty 
hours  at  o°.  At  the  end  of  this  time  the  solution,  which  should 
be  of  a  syrupy  consistency  and  pale  yellow  in  colour,  is  saturated 
with  common  salt  (to  render  the  aldol  less  soluble)  and  then 
extracted  at  least  four  times  with  ether,  the  ethereal  extracts 
dried  with  calcium  chloride,  and  the  ether  removed  by  distilla- 
tion from  the  water -bath.  The  crude  aldol,  which  is  often  red 
in  colour,  is  then  obtained  by  continuing  the  distillation  in 
vacua;  it  passes  over  at  8o°-9O°  at  20  mm.  pressure.  In 
carrying  out  the  distillation  it  is  advisable  to  insert  a  flask 
containing  concentrated  sulphuric  acid  between  the  receiver 
and  the  pump  in  order  to  absorb  aldehyde  vapours,  which 
would  otherwise  prevent  a  high  vacuum  being  obtained. 
The  yield  is  40  to  50  per  cent.  For  the  use  of  potassium  carbo- 
nate as  a  condensing  agent  in  the  above  preparation  the  reader 
is  referred  to  the  original  paper.1 

In  connection  with  the  aldol  condensation,  attention 
may  be  drawn  to  the  interesting  synthesis  of  sym.- 
triphenyl  benzene  by  passing  dry  hydrochloric  acid 
gas  into  acetophenone.  The  hydrocarbon  is  deposited 
after  standing  several  days  in  a  warm  place,  and  by 
resaturating  the  mother-liquors  yields  of  over  50  per 
cent,  are  said  to  be  obtained.2 


H2jCH 


Ph— C 


HC 


C— Ph 

ii'l 
o 


OL 

1 'V 


CH 
/ 


k 


1  M.  13,  516. 


CH 
•PhC      CPh 

— •  CH    CH 


C 

Ph 


2  B.  7,  1123. 


ALDEHYDES,    KETONES,   QUINONES  119 

V.    CONDENSATION     WITH     ETHYL    FORMATE. 

A  condensation,  analogous  to  the  formation  of  aceto- 
acetic  ester,  takes  place  under  the  influence  of  sodium 
ethoxide  between  ethyl  formate  and  compounds  con- 
taining the  group  —  CH2  —  CO  —  : 

CHO 

I 
R.CH2.CO.R  +  EtO.CHO  -  R.CH.CO.R  +  EtOH. 

PREPARATION  OF  ACETYL  ACETALDEHYDE 

(CHgCO.CHg.CHO).1  Thirty-four  grammes  of  dry,  freshly 
prepared  sodium  ethylate  (for  preparation,  see  p.  33)  are  sus- 
pended in  dry  ether  or  ligroin,  and  the  whole  cooled  with 
ice.  A  mixture  of  29  grm.  of  well-dried  acetone  and  37  grm. 
of  ethyl  formate  are  then  slowly  run  in,  the  whole  being 
well  stirred  during  the  process.  An  immediate  precipitation 
of  the  white  sodium  salt  of  acetyl  acetaldehyde  : 

CH3.C  :CH.CHO 

ONa 

takes  place.  This  is  collected,  washed  with  ether  or  ligroin, 
and  dried  in  a  vacuum  desiccator.  The  free  aldehyde  cannot 
be  isolated  as  it  at  once  condenses  to  sym.-tri  acetyl  benzene  : 

CH3.CO 

CH3CO 


oi 


CH 


CH3COC!H2i 


CH          — 


C.CO.CHg 


CH 


CH3COC 
\, 


CH 


C.COCH3 


PREPARATION      OF     CAMPHOR      ALDEHYDE      (Oxy- 

methylene  Camphor)  ,2  CaH1Ac    I  Twelve  and  a  half 

1  D.R.P.  45,367, 


l\  I 
\CH.CHO. 

2  D.R.P.  49,165. 


i2o      PREPARATION  OF  ORGANIC  COMPOUNDS 

grammes  of  sodium  wire  or  powder  are  added  to  a  solution  of 
176  grm.  of  camphor  dissolved  in  toluene.  The  whole  is  well 
cooled  with  ice,  and  then  37  grm.  of  ethyl  formate  added. 
After  standing  in  the  ice-chest  for  at  least  a  day  the  whole  is 
poured  into  ice-water  and  well  shaken.  The  aqueous  layer  is 
removed,  acidified  with  acetic  acid,  and  then  extracted  with 
ether.  The  ethereal  extract  is  dehydrated  with  calcium 
chloride,  and  the  greater  part  of  the  ether  removed  by  dis- 
tillation. The  residue  is  then  transferred  to  a  basin,  and 
allowed  to  evaporate  at  the  ordinary  temperature.  An  oil 
remains  which  on  standing  sets  to  a  solid,  crystalline  mass 
melting  at  76°-? 8°. 

VI.  REPLACEMENT  OF   HYDROGEN   BY  — CHO. 

In  the  last  section  a  method  was  described  whereby 
the  hydrogen  in  certain  aliphatic  compounds  could  be 
replaced  by  the  aldehydic  group.  In  the  aromatic 
series  this  result  can  also  be  brought  about  in  some 
cases.  The  oldest  and  best-known  method  consists 
in  treating  the  phenols  with  chloroform  and  caustic 
soda  (Reimer's  reaction).1  Phenolic  aldehydes  are 
thus  formed,  the  aldehydic  group  going  to  the  ortho-, 
and  to  a  less  extent  to  the  para-,  position  with  regard  to 
the  phenolic  group. 

PREPARATION    OF    o.-    AND    £.-OXYBENZ ALDEHYDE 

(C6H4(OH)CHO).2  Two  hundred  grammes  of  caustic  soda  are 
dissolved  in  320  c.c.  of  water  and  100  grm.  of  phenol  added. 
The  whole  is  heated  to  5O°-6o°  under  a  reflux  condenser, 
and  then  150  grm.  of  chloroform  slowly  dropped  in.  When  all 
the  chloroform  has  been  added,  the  whole  is  boiled  for  an  hour 
and  then  excess  of  chloroform  removed  by  distillation.  The 
contents  of  the  flask  are  made  strongly  acid  with  dilute 
sulphuric  acid,  and  then  steam-distilled.  The  distillate, 
which  consists  of  salicyl  aldehyde  and  phenol,  is  extracted  with 
ether,  and  the  ethereal  extract  well  shaken  with  concentrated 
sodium  bisulphite  solution.  The  bisulphite  compound  is 
collected,  washed  with  alcohol,  and  steam-distilled  with  dilute 
sulphuric  acid  or  sodium  carbonate.  The  aldehyde  is  isolated 
from  the  distillate  as  described  on  p.  1 1 6.  Yield  about  20  grm. 
The  £.-oxyaldehyde  is  in  the  residue  from  the  first  steam- 

i  Cf.  also  p.  i6|.  2  B.  9,  824. 


ALDEHYDES,   KETONES,   QUINONES  121 

distillation.  This  is  filtered  hot,  and  the  nitrate,  after  cooling, 
extracted  with  ether.  The  ether  is  removed  by  distillation, 
when  the  aldehyde  remains  as  a  mass  of  pale  yellow  needles. 
These  may  be  purified  by  recrystallisation  from  water,  and  melt 
at  ii5°-ii6°. 

The  following  methods  of  inserting  the  aldehyde 
group  into  the  benzene  nucleus  are  exceedingly 
interesting,  but  are  not  suitable  for  laboratory  prepara- 
tions : 

(i)  The  benzene  compound  is  treated  with  mercury 
fulminate  in  the  presence  of  anhydrous  aluminium 
chloride  containing  some  hydrated  chloride.  The 
reaction  takes  place  as  if  an  addition  compound  of 
fulminic  and  hydrochloric  acids  were  formed  : 

C1\  /H 

C6H6  +       )C  :  NOH  -  C6H5C/  +  HC1. 

H/ 


The  oxime  is  then  saponified.     B.  32,  3492  ;  36,  322. 

(ii)  The  phenol  or  phenolic  ether  is  treated  with 
anhydrous  hydrochloric  and  hydrocyanic  acids  in 
the  presence  of  aluminium  chloride.  The  reaction 
takes  place  as  if  an  addition  compound  of  the  acids 
were  formed  : 

H\  /H 

C6H5OH  +       >C  :  NH  =  C6H4(OH)(X  :  NH  +  HC1. 

CK 

The  imide  is  finally  saponified.     The  group  -C 


enters  the  para-  position   to   the  hydroxyl.     D  R.P. 

101,333- 

(iii)  The  hydrocarbon  is  treated  with  carbon  monoxide 
and  hydrochloric  acid  in  the  presence  of  cuprous  and 
aluminium  chlorides.  Here  the  reaction  takes  place 
as  if  the  unknown  formyl  chloride  were  first  formed. 
The  aldehydic  group  enters  the  para-  position. 

Cl 

C6H6CH8  +        >CO  =  C6H4(CH3)CHO  +  HC1. 
H/ 


T22      PREPARATION  OF  ORGANIC  COMPOUNDS 

Benzene  only  reacts  when  hydrobromic  acid  is  used, 
and  can,  therefore,  be  used  as  a  solvent.  D.R.P. 
126,421. 

B.  THE  KETONES 

I.  FROM    THE   ACIDS.      The  calcium   or,    better, 
the  barium  salts  of  the  carboxylic  acids  when  sub- 
mitted    to     destructive     distillation     yield     ketones. 
Mixed  ketones  can  also  be  obtained  by  this  method 
by  distilling  an  intimate  mixture  of  the  salts  of  two 
different  acids.     When  preparing  the  higher  members 
the  distillation  is  best  carried  out  in  vacuo. 

PREPARATION  OF  ACETONE  (CH3)2CO.  Five  hundred 
grammes  of  anhydrous  barium  acetate  are  placed  in  a  hard 
glass  or,  better,  a  metal  retort  connected  with  a  condenser, 
and  heated  with  a  free  flame  as  long  as  any  liquid  distils. 
The  distillate  is  shaken  for  four  or  five  hours  with  two  to 
three  volumes  of  saturated  sodium  bisulphite  solution.  The 
resulting  crystals  are  collected,  dissolved  in  water,  and  anhy- 
drous sodium  carbonate  added  until  an  alkaline  reaction  is 
obtained.  The  whole  is  then  distilled  from  the  water-bath, 
the  distillate  dried  with  calcium  chloride,  and  redistilled. 
Colourless  mobile  liquid  with  characteristic  smell.  B.P.  56°. 

II.  OXIDATION     OF     SECONDARY     ALCOHOLS. 

The  best  oxidising  agent  for  this  purpose  is  chromic 
acid  or  potassium  bichromate,  but  chlorine  water  and 
nitrous  acid  both  give  excellent  results  in  the  prepara- 
tion of  camphor  from  borneol  or  iso-borneol. 

The  oxidation  of  polyhydric  alcohols  to  the  corre- 
sponding ketones  is  best  carried  out  with  lead  peroxide 
and  sulphuric  acid,  or  Fenton's  reagent  (H2O2  and 
FeSO4).  The  aldose  phenylhydrazones  when  boiled 
with  phenyl  hydrazine  are  oxidised  to  osazones : 

CH2OH(CHOH)4.CH :  N.NHPh  +  2PhNH.NH2  = 

CH2OH(CHOH)3X 

>C:N.NHPh  +  PhNH2  +  H2O  +  NH3. 
PhNHN  :  CHK 

The  osone,  CH2OH(CHOH)3.CO.CHO,  can  then  be 


ALDEHYDES,    KETONES,  QUINONES  123 

liberated  by  boiling  with  acids.     Like  most  sugars, 
however,  they  are  troublesome  to  isolate. 

PREPARATION  OF  sym.-DICHLORACETONE,  (CH2Cl)2CO.i 
One  hundred  grammes  of  a-dichlorhydrin,  (CH2C1)2CHOH,  are 
mixed  with  80  grm.  of  finely  powdered  potassium  bichromate, 
and  the  whole  well  cooled  with  ice.  A  cold  mixture  of  120  grm. 
of  concentrated  sulphuric  acid  and  150  c.c.  of  water  are 
then  slowly  added  during  about  eight  hours.  The  reaction 
mixture  should  be  worked  up  at  once  and  not  allowed  to  stand 
over-night.  It  is  extracted  with  warm  concentrated  sodium 
bisulphite  solution,  and  the  bisulphite  compound  which 
separates  on  cooling  collected,  pressed  between  filter -paper, 
and  washed  with  a  little  ether.  It  is  suspended  in  a  little 
water,  ether  added,  and  then  the  calculated  quantity  of  sodium 
carbonate  in  concentrated  aqueous  solution  slowly  added  in 
several  portions.  The  liquid  must  be  well  shaken  after  the 
addition  of  each  portion,  and  the  ether  removed  and  replaced 
by  fresh  ether.  The  united  ethereal  extracts  are  dried  over 
calcium  chloride,  and  the  ether  distilled  off  from  the  water- 
bath.  The  residue  is  allowed  to  stand  in  vacua  over  con- 
centrated sulphuric  acid  until  crystallisation  takes  place, 
and  is  then  pressed  between  filter-paper,  dissolved  in  ether, 
and  the  ether  allowed  to  evaporate  at  the  ordinary  tempera- 
ture. The  ketone  then  separates  as  transparent  tablets 
which  melt  at  25°. 

PREPARATION  OF  BENZIL  (C6H5.CO.CO.C6H6).2 
Twenty-one  grammes  of  benzoin,  C6H5CO.CHOHC6H5,  are 
mixed  with  36  c.c.  of  concentrated  nitric  acid  (D  =  1-41) 
and  heated  on  the  water-bath  for  two  hours  under  a  reflux 
condenser.  The  whole  is  then  poured  into  water,  the  preci- 
pitated benzil  filtered  off,  washed,  and  finally  recrystallised 
from  alcohol.  Yellow  prisms  melting  at  95°.  Yield  about 
75  pev  cent. 

PREPARATION  OF  MENTHONE.3  Sixty  grammes  of 
potassium  bichromate  are  dissolved  in  300  c.c.  of  hot  water 
containing  50  grm.  of  sulphuric  acid.  The  solution  is  cooled 
to  30°  (at  which  temperature  crystallisation  begins)  and  45  grm. 
of  finely  powdered  menthol  added  all  at  once.  The  whole  is 

i  A.  208,  353.  2  A.  34,  188.  3  A.  250,   325. 


124      PREPARATION  OF  ORGANIC  COMPOUNDS 

violently  agitated,  and  soon  becomes  dark  in  colour,  and 
crystals  of  a  chromium-menthol  compound  separate  out. 
The  temperature  rises  spontaneously  and  is  maintained  at 
53°  by  cooling  or  warming  as  may  be  necessary.  The  double 
compound  gradually  decomposes,  a  precipitate  of  menthone 
being  deposited.  After  cooling,  the  whole  is  extracted  with 
ether,  the  ethereal  solution  washed  with  dilute  caustic  soda, 
and  the  ether  removed  by  distillation  from  the  water-bath. 
The  residual  menthone  is  steam-distilled  in  quantities  not 
exceeding  10  grm.  at  a  time,  collected,  and  dried  over  anhydrous 
sodium  sulphate.  It  forms  a  colourless  oil  boiling  at  206°. 
It  is  laevo-rotatory  ([a]D  =  -  28°),  and  is  converted  into  the 
dextro-  variety  by  concentrated  sulphuric  acid.  It  is  in  order 
to  avoid  this  change  that  less  than  the  calculated  quantity  of 
sulphuric  acid  is  used  in  the  oxidation,  and  that  the  temperature 
must  not  exceed  53°. 

Me.          H  Me.          H 


/  \ 

CH2      CH2  CH2      CH2 


CHOH  CH2  CO        CH2 

\   /  \  / 

CH  CH 

I  I 

CHMe2  CHMe2 

Menthol  Menthone 

PREPARATION  OF  CAMPHOR,  (a)  1  Fifteen  grammes  of 
borneol  are  dissolved  in  16  grm.  of  benzene  and  the  solution 
thus  obtained  shaken  with  900  c.c.  of  water  containing 
7- 1  grm.  of  chlorine  until  the  smell  of  chlorine  has  disappeared. 
The  benzene  layer  is  then  separated  and  the  benzene  removed 
by  distillation  from  the  water-bath.  Camphor  remains  behind 
in  almost  quantitative  yield. 

(b)  2  Nitrogen  trioxide  is  led  over  powdered  borneol  until 
the  whole  is  liquid  and  has  assumed  a  greenish  blue  colour. 
(This  should  be  done  under  a  reflux  condenser,  the  flask 
being  cooled  towards  the  end  of  the  treatment.)  The  liquid  is 
then  set  aside,  and  after  a  short  time  evolves  oxides  of  nitrogen, 
care  being  taken  that  the  temperature  does  not  exceed  70°. 

1  D.R.P.  177,290,  177,291,  179,738.  2  Ibid.  182,300. 


ALDEHYDES,   KETONES,  QUINONES  125 

When  the  reaction  is  over,  the  whole  is  poured  into  water,  and 
the  camphor  collected  by  filtration.  It  can  be  recrystallised 
from  alcohol.  M.P.  175°.  Yield  95  per  cent. 

CH2— CH— CH2  CH2— CH  —  CH2 


CMe2 


CMe9 


CH2— CMe— CHOH  CH2— CMe— CO 

Borneol  Camphor 

Ketonic  compounds  can  sometimes  be  obtained  from 
polyhydroxy-compounds  by  loss  of  water.  The  reac- 
tion is  usually  carried  out  by  heating  the  hydroxyl 
compound  with  acid  potassium  sulphate. 

PREPARATION  OF  PYRUVIC  ACID  (CH3CO.COOH).i 
Two  hundred  grammes  of  finely  powdered  acid  potassium 
sulphate  and  100  grm.  of  tartaric  acid  are  intimately  mixed  by 
grinding  them  together.  The  mixture  is  then  placed  in  a  large 
flask  and  distilled  from  an  oil -bath  at  220°  (no  higher).  Con- 
siderable frothing  takes  place  and  some  care  is  required  to 
prevent  boiling  over,  and  for  this  reason  the  apparatus  should 
be  arranged  so  that  the  flask  can  be  instantly  raised  clear  of 
the  oil-bath.  The  distillation  is  continued  until  nothing 
more  passes  over,  and  the  distillate  then  fractionated  under 
reduced  pressure.  The  pyruvic  acid  passes  over  at  68°-7O° 
at  20  mm.  and  forms  a  colourless  liquid  boiling  at  165°.  The 
yield  is  about  50  per  cent. 

JHolCHJCOO^H 

—     CH2:COH.COOH 
1C .  OH .  COOH  Enolic  form 

or          CH3.CO.COOH 
Ketonic  form 

CH2OH(CHOH)3 

\ 
PREPARATION  OF  d.-GLUCOSAZONE,2  PhNHN  :  C 

PhNHN  :  CH 
1  A.  242,  268.  2  B.  17,  579. 


126      PREPARATION  OF  ORGANIC  COMPOUNDS 

Ten  grammes  of  glucose,  fructose,  or  mannose,  or  a  corre- 
sponding amount  of  the  phenylhydrazones  of  these  sugars,  are 
mixed  with  20  grm.  of  phenyl  hydrazine,  dissolved  in  20  grm. 
of  50  per  cent,  acetic  acid  and  200  c.c.  of  water,  and  the  whole 
heated  on  the  water-bath  for  i£  to  2  hours.  The  d.-glucosa- 
zone  separates  out  in  yellow  needles  and  is  collected  and 
washed.  Yield  about  9  grm.  It  may  be  recrystallised  from 
dilute  alcohol,  and  melts  at  205°.  One  molecule  of  the  phenyl 
hydrazine  is  reduced  to  aniline,  which  may  be  recognised  in 
the  filtrate  by  the  bleaching-powder  reaction.  See  p.  122. 

III.  OXIDATION  OF  — CH2—  TO  —CO—.  This 
reaction,  as  a  rule,  can  only  take  place  when  the 
— CH2 —  group  is  attached  to  two  aromatic  residues. 
The  oxidation  is  best  carried  out  with  chromic  acid. 
For  indirect  method  via  the  zsonitroso  compounds,  see 
p.  130. 

/C°\ 
PREPARATION    OF    FLUORENONEi   (C6H4 C6H4). 

Ten  grammes  of  fluorene,  30  grm.  of  coarsely  ground  sodium 
bichromate,  and  40  grm.  of  glacial  acetic  acid  are  boiled  under 
a  reflux  condenser  for  two  to  three  hours.  The  whole  is  then 
poured  into  water,  and  the  precipitated  fluorenone  collected 
and  washed.  It  is  finally  recrystallised  from  rather  dilute 
alcohol.  It  forms  long  yellow  needles  melting  at  83°. 

/C°\ 
PREPARATION  OF  ANTHRAQUINONE  (C6H4<          >C6H4) . 

\XK 

Ten  grammes  of  anthracene  are  dissolved  in  120  c.c.  of  glacial 
acetic  acid  by  boiling  under  a  reflux  condenser.  A  solution 
obtained  by  dissolving  20  grm.  of  chromic  acid  in  15  c.c.  of 
water  and  then  diluting  with  75  c.c.  of  glacial  acetic  acid  is 
slowly  added  from  a  tap-funnel  during  an  hour,  the  liquid  in 
the  flask  being  kept  boiling.  When  all  the  chromic  acid  has 
been  added,  the  boiling  is  continued  for  ten  minutes  and  the 
deep  green  solution,  after  cooling,  poured  into  half  a  litre  of 
water.  The  precipitated  anthraquinone  is  collected,  well 
washed,  first  with  hot  water,  then  with  warm  dilute  caustic 
soda,  and  finally  again  with  water.  It  is  then  dried  in  the 
steam-oven.  Yield  about  10  grm.  It  is  best  purified  by 

i  A.  279,  258. 


ALDEHYDES,    KETONES,   QUINONES  127 

sublimation  at  250°.  Yellow  needles.  M.P.  277°.  If  crude 
anthracene  is  used,  the  crude  anthraquinone  should  be  purified 
by  heating  to  110°  for  ten  minutes  with  3  parts  of  5  per  cent. 
oleum  in  a  basin.  The  whole  is  then  allowed  to  stand  in  a 
damp  place  for  twenty-four  to  forty-eight  hours,  poured  into 
water,  filtered,  washed  with  boiling  dilute  caustic  soda,  and 
then  with  water,  dried,  and  finally  sublimed. 

IV.  CONDENSATION  OF  ACID  CHLORIDES  WITH 
BENZENE  DERIVATIVES.  This  condensation  forms 
a  standard  method  for  preparing  aromatic  ketones  and 
takes  place  under  the  influence  of  anhydrous  aluminium 
or  ferric  chlorides.  The  reaction  usually  occurs 
without  the  application  of  heat  and  is  carried  out  with 
or  without  a  solvent.  In  the  former  case  carbon 
bisulphide,  ligroin,  ether,  or  nitrobenzene  may  be  used. 
Further  discussion  will  be  found  on  pp.  42,  162. 

PREPARATION  OF  ACETOPHENONE  (C6H5CO .  CH,)  .1 
Thirty  grammes  of  benzene  are  poured  on  to  50  grm.  of  pow- 
dered aluminium  chloride  contained  in  a  flask  provided  with 
a  reflux  condenser.  Thirty-five  grammes  of  acetyl  chloride 
are  then  slowly  added  from  a  tap -funnel,  the  flask  being  cooled 
with  ice.  The  whole  is  then  set  aside  for  an  hour,  poured  on  to 
ice,  and  extracted  with  a  small  quantity  of  benzene.  The 
benzene  layer  is  washed,  first  with  dilute  caustic  soda  and  then 
with  water.  It  is  dehydrated  with  calcium  chloride  and  dis- 
tilled. The  fraction  boiling  at  i9O°-2io°  is  collected  and 
redistilled.  The  acetophenone  then  passes  over  as  a  sweet- 
smelling  oil  boiling  at  202°,  and  on  standing  solidifies  to  a 
crystalline  mass  melting  at  20°.  Yield  about  50  per  cent. 

PREPARATION      OF     ACET-SALICYLIC      ACID 

(C6H3[i]OH[2]COOH[4]COCH3).2  Eighty  grammes  of  sali- 
cylic acid  are  mixed  with  100  grm.  of  acetyl  chloride,  and 
100  grm.  of  sublimed  ferric  chloride  added  little  by  little. 
A  brisk  reaction  takes  place  and  the  O. -acetyl  derivative, 
"aspirin,"  C6H4(OCOCH3)  (COOH),  is  first  formed.  Further 
addition  of  ferric  chloride  causes  the  mass  to  become  liquid 
again  and  to  assume  a  dark  brown  colour.  When  the  evolution 
of  hydrochloric  acid  slackens  the  whole  is  cautiously  warmed 

i  A.  Ch.  [6]  I,  507  ;    14,  455.  2  B.  30,  1776. 


128      PREPARATION  OF  ORGANIC  COMPOUNDS 

over  a  free  flame,  the  flask  being  continuously  shaken,  to  iio°, 
but  care  must  be  taken  not  to  exceed  this  temperature.  The 
heating  is  continued  for  a  quarter  of  an  hour  after  all  the 
ferric  chloride  has  been  added,  and  the  melt  then  poured  into 
a  basin  and  allowed  to  cool.  It  is  washed  three  times  with 
cold  water,  the  residue  dissolved  in  boiling  water  and  filtered 
hot.  Hydrochloric  acid  is  added  to  the  hot  filtrate  until 
the  deep  red  colour  disappears.  The  acet-salicylic  acid 
separates  out  on  cooling  in  yellow  needles,  which  after  standing 
for  twenty-four  hours  are  collected,  washed,  and  recrystallised 
from  alcohol.  If  still  coloured  it  should  be  boiled  with  a 
little  water  to  which  a  crystal  of  potassium  permanganate 
has  been  added.  M.P.  210°.  Yield  about  25  per  cent. 

PREPARATION    OF    £.2-DIMETHYL    BENZOPHENONE 

(CH3[4]C6H4[i]CO[i/]C6H4[4/]CH3).i  A  litre  flask  is  provided 
with  a  double-bored  cork  carrying  a  wide  glass  tube,  or,  better, 
a  wide-stemmed  ordinary  conical  funnel  closed  with  a  well- 
fitting  cork,  and  a  reflux  condenser  provided  with  an  absorp- 
tion apparatus  as  in  Fig.  47,  p.  51.  The  absorption  liquid 
consists  of  toluene,  and  should  be  cooled  with  ice  or  a  freezing 
mixture.  Two  hundred  grammes  of  a  technical  20  per  cent. 
toluene  solution  of  carbonyl  chloride  are  placed  in  the  flask, 
and  100  grm.  of  powdered  aluminium  chloride  slowly  added 
through  the  wide  glass  tube  or  funnel.  The  addition  requires 
about  four  hours,  and  the  funnel  should  be  closed  after  each 
portion  has  been  added,  in  order  that  the  carbonyl  chloride 
driven  off  by  the  reaction  may  be  collected  in  the  toluene. 
During  the  addition  the  flask  should  be  cooled  in  a  water-bath. 
When  all  the  aluminium  chloride  has  been  added,  the  flask  is 
warmed  very  gently  for  a  short  time,  and  the  contents  then 
slowly  poured  into  water  and  distilled  in  steam  until  nothing 
more  passes  over.  The  aqueous  part  of  the  residue  is  then 
poured  off  as  far  as  possible  and  discarded,  very  dilute  hydro- 
chloric acid  added  to  the  solid  matter,  and  the  whole  distilled 
in  steam  for  half  an  hour.  The  aqueous  portion  is  again 
discarded,  the  solid  matter  well  washed,  and  then  either 
fractionally  distilled  or  recrystallised  several  times  from 
dilute  alcohol.  The  ketone  forms  colourless  needles  melting 
at  94°-95°  and  boiling  at  333°.  The  yield  is  50  to  80  per 
cent. 

i  A.  312,  92  ;  B.  7,  1183  ;   IO,  2173  ;   J.  pr.  [2]  35,  466. 


ALDEHYDES,  KETONES,  QUINONES  129 

V.  CONDENSATION  OF  PHTHALIC  ANHYDRIDE 
WITH  BENZENE,  ETC.  Phthalic  anhydride  condenses 
readily  with  benzene  and  its  derivatives  to  form 
benzoyl  benzoic  acids  : 

/COX  A1C13 


C6H4 


Nxx 


C6H5CO.C6H4COOH 


and  these  readily  lose  water  to  form  the  corresponding 
anthraquinone  : 


/\/C°\ 


\ 


-co 


\/\ 


COjOHj 


/\/"W\/\ 


\/\CO/\/ 


H0. 


This  method  may  become  of  considerable  technical 
importance,  as  phthalic  anhydride  can  be  obtained 
cheaply  from  naphthalene,  and  anthraquinone  is  in 
increasing  demand  for  the  preparation  of  the  new  vat- 
dyes,  such  as  indanthrene. 

PREPARATION      OF      o.-BENZOYL       BENZOIC     ACID 

(C6H5CO[i]C6H4[2]COOH).i  Fifty  grammes  of  finely  pow- 
dered phthalic  anhydride  are  added  to  175  grm.  of  dry  benzene, 
and  90  grm.  of  powdered  aluminium  chloride  then  added 
all  at  once.  The  whole  is  gradually  warmed  on  the  water- 
bath  in  a  flask  fitted  with  a  reflux  condenser  and  mechanical 
stirrer.  The  reaction  starts  at  30°,  and  is  prevented  from 
becoming  too  violent  by  regulating  the  temperature  of  the 
water-bath.  When  the  mass  has  become  too  viscous  for  the 
stirrer  to  revolve,  the  temperature  is  gradually  raised  to 
70°  and  maintained  at  this  point  until  no  more  hydrochloric 
acid  is  evolved.  The  condenser  is  then  inverted  and  cold  water 
slowly  added.  Considerable  heat  is  evolved  and  the  greater 
part  of  the  unchanged  benzene  distils  off.  The  rest  is  removed 
with  steam,  and  the  residue  boiled  for  several  hours  with  excess 
of  sodium  carbonate.  The  alumina  is  then  filtered  off  and  well 
washed  with  boiling  water.  On  treating  the  cooled  nitrate  with 
hydrochloric  acid,  benzoyl  benzoic  acid  is  precipitated  in  almost 

1  A.  291,  9  ;  C,  r.  119,  139. 


130      PREPARATION  OF  ORGANIC  COMPOUNDS 

quantitative  yield.  It  may  be  recrystallised  from  xylol  or 
water.  From  the  latter  solvent  it  separates  in  long  needles 
containing  one  molecule  of  water,  wh,ich  it  loses  at  1 10°.  The 
hydrated  acid  melts  at  94°,  the  anhydrous  acid  at  127°. 

PREPARATION      OF      ANT  H  R  A  Q  UI  NO  N  E,1 

/C°\ 
C6H4<'          /C6H4.      Twenty  grammes  of  o.-benzoyl  benzoic 

XXX 

acid  are  mixed  with  120  grm.  of  concentrated  sulphuric  acid 
and  heated  on  the  oil-bath  to  150°  for  one  hour.  After 
cooling,  the  whole  is  poured  on  to  ice  and  the  precipitated 
anthraquinone  collected  and  purified  as  described  on  p.  126. 
The  yield  is  quantitative. 

VI.  FROM  THE  iso-NITROSO-COMPOUNDS.  This 
forms  a  useful  method  for  obtaining  a-diketones.  The 
^'so-nitroso-compounds  are  obtained  from  the  mono- 
ketones  containing  the  group  — CH2 — CO —  as  de- 
scribed on  p.  198. 

/CO 

PREPARATION    OF    CAMPHORQUINONE,2    C8H14/  | 

\CO 

Nine  grammes  of  z'so-nitroso  camphor  are  dissolved  in  15  c.c. 
of  glacial  acetic  acid  and  a  solution  of  4  grm.  of  sodium 
nitrite  in  8  c.c.  of  water  very  slowly  added,  the  whole  being 
violently  stirred  or  shaken.  The  solution  at  first  becomes 
brown  and  then  greenish  in  colour,  and  nitrous  oxide  is  evolved, 
but  there  should  be  no  smell  of  nitrous  acid.  Heat  is  evolved, 
and  much  rise  in  temperature  must  be  prevented  at  the  begin- 
ning of  the  preparation  by  cooling  from  time  to  time  in  water. 
Towards  the  end  of  the  operation  the  evolution  of  gas  slackens, 
and  the  reaction  must  then  be  assisted  by  heating  over  a  naked 
flame.  When  no  more  gas  is  evolved,  the  contents  of  the 
flask  are  allowed  to  cool  and  then  poured  into  excess  of  cold 
water.  The  quinone  is  precipitated  as  a  crystalline  mass 
which,  after  washing  and  drying,  can  be  purified  by  sublimation 
at  60°.  It  forms  golden-yellow  sweet-smelling  needles  which 
melt  at  198°.  Yield  50  per  cent. 

/C :  NOH  /CO 

CeH14<   |  +  HNOo  =  C8H14<   |     +  N20  +  H2O. 

XCO  XCO 

1  Z.  a.  Ch.  19,  669.  2  A.  274,  71. 


ALDEHYDES,   KETONES,   QUINONES  131 

VII.  FROM  AROMATIC  ALDEHYDES.  Aromatic 
aldehydes,  in  which  the  aldehydic  group  is  directly 
attached  to  the  ring,  undergo  a  peculiar  condensation 
when  heated  with  alcoholic  solutions  of  potassium 
cyanide.  The  action  of  the  cyanide  is  catalytic,  a 
small  quantity  being  able  to  convert  a  large  quantity 
of  the  aldehyde  into  the  corresponding  benzoin.  The 
course  of  the  reaction  is  probably  the  alternate  forma- 
tion and  decomposition  of  a  cyanhydrin  : 

XOH 
Ph.CHO  +  HCN  -  PhC^-H 

\CN 

/OH  *O  /OH      /OH 

PhC-H      +  Phcf      =  PhC^  -  C-Ph 
XH  \CN 


XOH       /OH 

^  -  C^Ph  =  PhCO.CHOH.Ph  +  HCN 
\CN      XH 

It  will  be  seen  that  the  resulting  benzoin  is  a  hydroxy- 
ketone.  The  benzoin  condensation  has  not  been 
observed  in  the  aliphatic  series,  but  is  general  for 
aromatic  aldehydes,  and  is  also  undergone  by  some 
heterocyclic  aldehydes,  such  as  furfurol. 

PREPARATION  OF  BENZOIN  (C6H5CO  .  CHOHC6H5)  .1 
Fifty  grammes  of  benzaldehyde  are  dissolved  in  100  c.c.  of 
alcohol,  and  about  10  grin,  of  potassium  cyanide  in  twice  its 
weight  of  water  added.  The  whole  is  then  refluxed  on  the 
water-bath  for  an  hour.  On  cooling,  the  benzoin  crystallises 
out  and  is  filtered  off  and  washed  with  a  little  alcohol.  Thus 
obtained  it  is  quite  pure  enough  for  the  preparation  of  benzil 
(p.  123),  but  if  desired  it  can  be  recrystallised  from  dilute 
alcohol.  It  forms  colourless  prisms  melting  at  137°. 

VIII.  CLAISEN'S  REACTION.  Claisen's  reaction 
consists  in  the  splitting  out  of  a  molecule  of  alcohol 
from  an  ester  and  a  second  component  which  may  be 

1  A.  34,  186  ;    198,  151. 


132      PREPARATION  OF  ORGANIC  COMPOUNDS 

(a)  another  molecule  of  the  same  ester,  (b)  a  different 
ester,  (c)  a  ketone. 

RCOOEt  +  R.CH2.COOEt  =  RCO.CHRCOOEt 
RCOOEt  +  HCR2COCR3  =RCO.CR2.COCR3 

where  R  may  be  hydrogen,  or  an  alkyl  or  aryl  group. 

It  is  only  the  a-hydrogen  atom  of  the  second  com- 
ponent, i.e.  the  hydrogen  atom  on  the  carbon  next  to 
the  carboxylic  or  ketonic  group,  that  reacts,  and 
hence,  in  case  (a)  only  those  esters  which  contain  such 
an  hydrogen  atom  undergo  the  condensation.  The 
reaction  always  gives  rise  to  /3-diketonic  compounds 
and  is  the  general  case  of  the  formic  ester  condensation 
mentioned  on  p.  119.  The  condensation  is  brought 
about  by  metallic  sodium,  sodium  ethylate,  or  soda- 
mide.  The  latter  reagent,  which  is  of  fairly  recent 
application,  often  gives  excellent  results. 

PREPARATION  OF  ACETO ACETIC  ESTER  (CH3CO.CH2. 
COOEt).1  Two  hundred  and  fifty  grammes  of  ethyl  acetate, 
which  have  been  dehydrated  over  calcium  chloride,  are  placed 
in  a  flask  fitted  with  a  reflux  condenser,  and  25  grm.  of  sodium, 
either  in,  thin  slices  or,  better,  as  wire,  added .  When  the 
vigorous  reaction  which  at  first  sets  in  has  slackened,  the  whole 
is  boiled  until  all  the  sodium  has  vanished.  The  warm  liquid 
is  then  acidified  with  50  per  cent,  acetic  acid  (about  160  c.c. 
will  be  required)  and  shaken  with  400  c.c.  of  saturated  salt 
solution.  After  standing  a  few  minutes  the  liquid  separates 
into  two  layers,  the  upper  one  of  which  is  collected,  and  frac- 
tionated in  vacua  until  a  fraction  boiling  constantly  at  71° 
at  13  mm.  pressure  is  obtained.  Colourless  liquid  with 
pleasant  smell  boiling  at  181°  at  atmospheric  pressure.  Yield 
about  35  per  cent. 

Propiopropionic  ester  is  obtained  in  the  same  way, 
but  the  higher  esters  do  not  undergo  the  condensation. 
Succinic  ester  behaves  like  acetic  ester,  but  being 
dibasic  gives  a  cyclic  compound. 

PREPARATION    OF    SUCCINOSUCCINIC     ESTER."     Ten 

grammes  of  granulated  sodium   (p.  33)   are  added  to  38  grm. 
1  A.  186,  161,  214.  2  A.  211,  308  ;   229,  45. 


ALDEHYDES,  KETONES,   QUINONES  133 

of  ethyl  succinate  containing  two  or  three  drops  of  absolute 
alcohol,  and  the  whole  set  aside  for  ten  days .  The  dry  mass  is 
then  broken  up,  and  made  faintly  acid  with  dilute  hydrochloric 
acid.  The  insoluble  portion  is  collected  and  recrystallised 
from  alcohol.  M.P.  126°.  Yield  excellent. 

COOEt  COOEt 

CHJH  EtOJ  CH 

CH9  CO  CH9        CO 


CO  CH2  CO          CH2 

\               /  \      / 

lOEtl  /  CH 

HiCH 

'! '  |  COOEt 

COOEt 

2  molecules  succinic  ester  Succinosuccinic  ester 

PREPARATION  OF  ACETYL  ACETONE  (CH3CO. 
CH2COCH3).i  Ethyl  acetate  (120  c.c.)  is  dissolved  in  32  c.c. 
of  pure  dry  acetone,  and  the  whole  cooled  in  a  freezing  mixture. 
Thirty-five  grammes  of  finely  powdered  sodamide  are  then 
slowly  added.  The  reaction  sets  in  at  once  and  ammonia 
is  evolved.  When  all  the  sodamide  has  been  added  the  whole 
is  allowed  to  stand  some  time  at  o°  and  then  over-night  at  the 
ordinary  temperature.  Ice-water  is  then  added  and  the 
aqueous  layer  removed.  This,  on  acidifying  with  acetic  acid 
and  subsequent  addition  to  concentrated  copper  acetate 
solution,  gives  a  deep  blue  precipitate  of  the  copper  salt, 
(  (CH3CO)2CH)2Cu.  Yield  25  grm.  The  free  diketone  can  be 
obtained  from  this  by  shaking  it  with  chloroform  and  dilute 
sulphuric  acid.  The  chloroform  layer  is  dried,  and  after  the 
chloroform  has  been  removed  on  the  water-bath,  the  diketone 
passes  over  at  i35°-i42°. 

PREPARATION  OF  ACETYL  ACETOPHENONE  (CH8CO. 
CH2COC6H6).2  Twenty-four  grammes  of  acetophenone  and 
19  grm.  of  ethyl  acetate  are  dissolved  in  150  c.c.  of  absolute 

i  B.  38,  695  ;  D.R.P.  49,542.  2  Loc.  cit. 


134      PREPARATION  OF  ORGANIC  COMPOUNDS 

ether,  and  16  grm.  of  powdered  sodamide  slowly  added.  After 
a  few  hours  the  whole  sets  to  an  almost  solid  mass  of  the  sodium 
salt.  It  is  set  aside  for  a  day  and  then  poured  on  to  sufficient 
ice-water  to  dissolve  the  whole  of  the  precipitate.  The  aqueous 
layer  is  separated,  and  freed  from  dissolved  ether  by  blowing  a 
current  of  air  through  it.  On  acidifying,  the  acetyl  benzo- 
phenone  is  precipitated  in  77  per  cent,  yield.  M.P.  6o°-6i°. 

Higher  members  may  be  built  up  from  acetoacetic 
ester,  &c.,  by  condensing  with  alkyl  or  acyl  halides  : 

CH3CO.CH— COOEt  ;         CH3CO . CH— COOEt. 

CO.R 

These  compounds  can  then  condense  with  another 
halogen  compound  giving,  for  example, 

CH3COCR2COOEt. 

All  these  substances  on  boiling  with  dilute  caustic 
potash  undergo  the  "  ketonic  hydrolysis,"  forming 
alcohol,  carbon  dioxide,  and  a  ketone  : 

CH3CO.CR2COOEt  +  H20  =* 

CH3COCHR2  +  EtOH  +  C02. 

The  "  acid  hydrolysis  "  with  concentrated  potash 
will  be  found  discussed  on  p.  170. 

In  the  same  way  ketonic  acids  can  be  obtained  by 
condensing  malonic  ester  with  one  or  two  molecules 
of  an  acid  chloride  and  then  hydrolysing  the  product : 

R.CO.CH(COOEt)2  +H2O  = 

R.CO.CH2.COOH  +  EtOH  +  CO2. 

PREPARATION  OF  MONO-  AND  DI-ETHYL  ACETO- 
ACETIC ESTER.1  Twenty-three  grammes  of  sodium  are  slowly 
added  to  300  c.c.  of  absolute  alcohol  contained  in  a  flask 
fitted  with  a  reflux  condenser.  When  all  the  sodium  has 
dissolved,  the  solution  is  cooled  with  ice,  and  130  grm.  of 
acetoacetic  ester  added.  One  hundred  and  seventy  grammes 

i  A.  186,  188. 


ALDEHYDES,   KETONES,  QUINONES  135 

of  ethyl  iodide  are  then  slowly  dropped  in.  When  all  the 
iodide  has  been  added,  the  whole  is  heated  until  neutral  to 
moist  litmus  paper.  To  bring  this  about  it  may  be  necessary 
to  add  a  little  more  ethyl  iodide.  When  neutral,  the  solution, 
which  now  contains  monoethyl  acetoacetic  ester,  is  divided  into 
two  equal  parts.  From  one  part  the  alcohol  is  removed  by 
distillation  on  the  water-bath,  the  residue  shaken  with  water 
until  all  the  solid  matter  is  dissolved,  and  then  extracted  with 
ether.  The  ethereal  solution  is  dehydrated  with  anhydrous 
sodium  sulphate,  and  the  ether  distilled  off  from  the  water- 
bath.  The  residue  is  then  fractionated  in  vacua.  B.P. 
82°-84°  at  14  mm.,  198°  at  760  mm.  Yield  60  to  80  per  cent. 

The  second  part  is  converted  into  the  diethyl  compound 
by  adding  a  solution  of  nj  grm.  of  sodium  in  150  c.c. 
alcohol,  and  then  slowly,  as  before,  85  grm.  of  ethyl  iodide. 
The  whole  is  boiled  until  neutral  and  the  diethyl  compound 
isolated  in  exactly  the  same  way  as  the  monoethyl  derivative. 
B.P.  94°-95°  at  1 6  mm.,  204°  at  760  mm.  Yield  50  to  60  per 
cent. 

PREPARATION   OF    BENZOYL  ACETOACETIC  ESTER,* 

COC6H5 

Sodium  (35-4  grm.)  is  slowly  added  to 
CHgCO.CH.COOEt. 

600  c.c.  of  absolute  alcohol  under  a  reflux  condenser.  When 
all  the  sodium  has  dissolved,  the  liquid  is  cooled  and  300  c.c. 
of  it  drawn  off.  To  this  is  added  100  grm.  of  acetoacetic  ester. 
Ninety  cubic  centimetres  of  benzoyl  chloride  are  placed  in 
a  burette,  and  with  continual  stirring  45  c.c.  allowed  to  run 
slowly  into  the  mixture  of  acetoacetic  ester  and  sodium 
ethylate.  The  addition  should  take  fifteen  minutes  and  the 
temperature  must  be  kept  below  10°.  The  whole  is  allowed 
to  stand  for  half  an  hour,  and  then  1 50  c.c.  of  the  ethylate  solu- 
tion and  22-5  c.c.  of  benzoyl  chloride  added  exactly  as  before. 
This  treatment  is  repeated,  always  halving  the  amount  of 
ethylate  and  benzoyl  chloride,  until  all  the  ethylate  solution 
and  chloride  have  been  used.  After  twelve  hours  the  sodium 
salt  is  filtered  off  and  washed  with  ether.  By  treating  it  with 
ice-water  and  dilute  acetic  acid  the  free  ketone  can  be  obtained. 
It  is  extracted  with  ether,  dehydrated  with  anhydrous  sodium 
sulphate,  and  the  ether  removed  by  distillation  from  the  water  - 

1  A.  226,  220  ;  291,  71. 


136     PREPARATION  OF  ORGANIC  COMPOUNDS 

bath.  The  residue  is  then  fractionated  under  as  high  a  vacuum 
as  possible.  At  12  mm.  it  passes  over  at  175°  with  only  very 
slight  decomposition.  It  forms  a  thick  liquid. 

The  monoalkyl  acetoacetic  esters  prepared  as  above 
are  often  contaminated  with  the  dialkyl  compounds. 
This  is  due  to  double  decomposition  taking  place 
between  the  unchanged  sodium  salt  and  the  mono- 
alkyl ester  : 

CH3COCHNaCOOEt  +  CH3CO.CHR.COOEt  = 

CH3COCH2COOEt  +  CH3COCNaRCOOEt. 

This  can  be  remedied  to  a  large  extent  by  using  only 
half  the  calculated  quantity  of  sodium  and  alkyl 
halide.  Of  course  under  these  conditions  half  the 
acetoacetic  ester  remains  unchanged,  but  this  is  readily 
recovered  by  distillation. 

PREPARATION  OF  BENZYL  ACETOACETIC  ESTER 
(CHjjCOCHBzCOOEt).1  A  solution  of  5-75  grm.  of  sodium  in 
75  c.c.  of  alcohol  is  added  to  65  grm.  of  acetoacetic  ester. 
Benzyl  chloride  (31-8  grm.)  is  then  added,  and  the  whole,  after 
standing  for  an  hour  at  30°,  boiled  under  a  reflux  condenser 
for  an  hour.  The  product  is  then  fractionated  in  vacuo.  The 
benzyl  acetoacetic  ester  passes  over  at  i64°-i65°  at  14  mm. 
The  yield  is  about  89  per  cent.,  allowing  for  the  acetoacetic 
ester  recovered. 

PREPARATION  OF  METHYL  zso-AMYL  KETONE 
(CH3.CO.CH(C2H5)2).2  Diethyl  acetoacetic  ester  is  boiled 
under  a  reflux  condenser  with  saturated  baryta  water,  or 
alcoholic  potash.  The  product  is  carefully  washed  with 
saturated  salt  solution  until  free  from  alcohol,  dried  with 
calcium  chloride,  and  distilled.  The  ketone  forms  a  colourless 
mobile  liquid  boiling  at  137°-! 39°. 

Methyl  Propyl  Ketone  3  can  be  prepared  in  exactly  the  same 
way  from  monoethyl  acetoacetic  ester.  It  is  best  purified 
by  means  of  the  bisulphite  compound.  It  boils  at  101°. 

1  B.  44,   1507.  2  A.  138,  211.  3  Loc.  cit. 


ALDEHYDES,   KETONES,   QUINONES  137 

C.  THE  QUINONES  AND  QUINONE-IMIDES 

The  quinones  can  be  roughly  divided  into  three 
classes,  viz.  (a)  ortho-quinones,  (b)  ^am-quinones,  (c) 
quinones  in  which  the  quinonoid  groups  are  on 
different  nuclei,  e.g.  : 

O 


V 

II 

O 

Pyrenequinone 

These  last  are  of  but  little  interest  and  will  not  be 
further  considered.  The  quinone-imides  are  quinones 
in  which  either  or  both  of  the  quinonoid  oxygen 
atoms  have  been  replaced  by  the  imino-group,  =NH. 
The  quinone-imides  themselves  are  usually  unstable 
and  difficult  to  isolate,  but  their  chlorides,  which 
contain  =N.C1  in  place  of  =NH,  are  often  easily 
obtained. 

The  quinones  and  quinone-imides  are  invariably 
obtained  by  oxidation,  and  a  large  variety  of  sub- 
stances serve  as  starting-out  points  for  their  prepara- 
tion. 

(a)  HYDROCARBONS.  This  method  is  only  appli- 
cable to  polynuclear  quinones.  The  preparation  of 
anthraquinone  is  the  best-known  example  and  was 
discussed  on  p.  126.  a-Naphthoquinone  can  also  be 
prepared  by  this  method,  but  the  procedure  described 
on  p.  140  gives  better  yields. 


38      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  a-NAPHTHOQUINONE.1  Ten  grammes 
of  chromic  acid  are  dissolved  in  65  c.c.  of  ice-cold  So  per  cent. 
acetic  acid.  A  solution  of  10  grm.  of  naphthalene  in  95  c.c. 
of  glacial  acetic  acid  is  then  slowly  added,  and  the  whole 
allowed  to  stand  for  three  days  at  the  ordinary  temperature 
with  occasional  shaking.  At  the  end  of  this  time  the  liquid 
is  poured  into  850  c.c.  of  water,  and  the  precipitated  quinone 
filtered  off.  It  is  almost  pure,  but  may  be  purified  by  subli- 
mation or  by  recrystallisation  from  alcohol.  It  forms  golden- 
yellow  plates  which  melt  at  125°.  It  possesses  a  biting 
odour  and,  like  all  true  quinones,  is  very  volatile  with  steam. 
Yield  about  40  per  cent. 

(b)  PRIMARY  AMINES.  The  oxidation  of  the  primary 
amines  with  sodium  or  potassium  bichromate  is  the 
standard  method  of  preparing  the  quinones  of  the 
benzene  series.  The  method  is  also  applicable  to 
a-naphthylamines,  but  does  not  give  satisfactory 
yields.  Sulphonic  acid  groups  if  present  in  the  ^im- 
position are  split  out.  Thus  sulphanilic  acid  on  oxida- 
tion gives  />.-benzoquinone. 

PREPARATION  OF  BENZOQUINONE  (O  :  C6H4 :  O)  .2 
One  hundred  grammes  of  aniline  are  dissolved  in  2  litres 
of  water  containing  800  grm.  of  concentrated  sulphuric  acid. 
One  kilogramme  of  ice  is  added,  and  when  the  temperature  has 
fallen  below  o°,  a  cold  saturated  solution  of  300  grm.  of  sodium 
dichromate  is  slowly  run  in.  During  this  addition,  which 
requires  about  five  hours,  the  whole  must  be  continually 
stirred,  and  the  temperature  must  be  kept  below  5°.  When 
all  the  dichromate  has  been  added  the  whole  is  allowed  to 
stand  quietly  for  an  hour,  at  the  end  of  which  time  the  quinone 
will  have  risen  to  the  surface.  It  is  skimmed  off,  filtered, 
washed  with  a  little  cold  water,  and  dried  between  filter-paper. 
It  must  not  be  dried  in  the  oven  or  in  a  vacuum  desiccator.  It 
is  then  purified  by  recrystallisation  from  ligroin  in  a  Soxhlet 
apparatus.  It  forms  long  yellow  needles  which  have  a  biting 
odour,  are  very  volatile,  and  melt  at  116°.  Yield  60  per  cent. 
By  extracting  the  dark-coloured  liquid  with  ether  a  further 
quantity  can  be  obtained,  bringing  the  yield  up  to  85  per 
cent. 

i  Soc.  37,  634;    A.  167,  357.  2  B.  20,  2283. 


ALDEHYDES,  KETONES,   QUINONES  139 

As  a  rule,  ^.-diamines  are  more 
readily  oxidised  to  quinones  than  are  the  monamines. 
Thus  i.4-naphthylene  diamine  on  treatment  with 
hydrochloric  acid  and  sodium  nitrite  at  a  low  tempera- 
ture is  oxidised  to  a-naphthoquinone,  no  trace  of  diazo- 
compound  being  formed.  In  carrying  out  the  pre- 
paration, it  is  merely  necessary  to  filter  off  the  quinone 
and  then  recrystallise  it.  The  ^.-diamines  are  readily 
obtained  by  reducing  the  corresponding  azo-colours. 
See  p.  214. 

PREPARATION  OF  CHLORANIL  (O  :C6C14 : 0).i 
Twenty-four  grammes  of  2.6-dichlor-4-nitraniline  are  reduced 
to  the  corresponding  diamine  by  boiling  with  600  c.c.  of 
concentrated  hydrochloric  acid  and  26  grm.  of  tin.  Without 
cooling,  20  grm.  of  crystallised  potassium  chlorate  are  slowly 
added,  the  whole  being  kept  gently  boiling.  The  boiling  is  con- 
tinued for  a  few  minutes  after  the  whole  of  the  chlorate  has 
been  added,  and  the  liquid  then  diluted  and  filtered.  The 
precipitate  is  well  washed  with  water,  dried,  and  then  purified 
either  by  recrystallisation  from  toluene  or  by  sublimation. 
Yellow  leaflets  which  sublime  on  heating.  Yield  90  per  cent. 
The  potassium  chlorate  acts  simultaneously  as  an  oxidising 
and  chlorinating  agent : 


Cll 


NH2 

/\ 

Cl 


t 

cil 


+  KC1+H2O+2NH4C1. 
Cl 


NH2  || 

O 
Chloranil 

AMINO-PHENOLS.  The  o.-  and  ^.-amino-naphthols 
and  the  ^.-amino-phenols  are  very  readily  oxidised 
to  the  corresponding  quinones,  and  as  the  amino- 
phenols  are  readily  obtained  from  the  phenols 
either  by  reducing  the  nitroso  -  compounds  or 
by  first  forming  an  azo- colour  and  then  reducing 

i  B.  36,  4390. 


1 40      PREPARATION  OF  ORGANIC  COMPOUNDS 

this  (p.  214),  their  oxidation  forms  one  of  the  easiest 
methods  of  preparing  quinones.  The  oxidation  is 
usually  brought  about  by  nitrous  or  nitric  acid,  but 
bichromate,  lead  peroxide,  &c.,  may  also  be  used. 

PREPARATION  OF  a-NAPHTHOQUINONE  (1.4).!  Fifty 
grammes  of  amino-naphthol  or  a  corresponding  amount  of 
one  of  its  salts  (obtained  by  the  reduction  of  Orange  I,  p.  216) 
are  suspended  in  200  c.c.  of  10  per  cent,  hydrochloric  acid, 
and  40  grm.  of  sodium  nitrite  slowly  added.  The  resulting 
yellow  precipitate  is  collected,  and  purified  either  by  steam 
distillation,  sublimation,  or  by  recrystallisation  from  ligroin 
or  alcohol.  Yellow  plates  melting  at  125°.  Yield  about 
70  per  cent.  A  further  quantity  can  be  obtained  by  extracting 
the  mother-liquors  with  ether. 

PREPARATION  OF  /3-NAPHTHOQUINONE  (1-2) .2  Thirty 
grammes  of  a-amido-/3-naphthol  (obtained  by  the  reduction 
of  Orange  II — Mandarin,  pp.  216,  250)  are  suspended  in  120  c.c. 
of  water  containing  30  c.c.  of  concentrated  sulphuric  acid. 
The  whole  is  cooled  to  o°  by  the  addition  of  ice,  and  then 
15  grm.  of  potassium  or  sodium  bichromate  dissolved  in  200  c.c. 
of  water  slowly  added.  The  mixture  must  be  well  stirred, 
and  any  rise  in  temperature  prevented  by  adding  more  ice 
from  time  to  time.  The  quinone  separates  in  the  pure  state 
and  only  requires  to  be  carefully  washed.  Red  needles 
melting  with  decomposition  at  115°-! 20°. 

PREPARATION  OF  /3-NAPHTHOQUINONE-4-SULPHONIC 
ACID.  Twenty  grammes  of  a-amino-/3-naphthol-4-sulphonic 
acid  are  ground  up  with  30  c.c.  of  23  per  cent,  nitric  acid. 
When  the  reaction  is  over,  hot  water  is  added  until  solution 
takes  place.  Some  insoluble  impurities  are  removed  by 
nitration,  and  the  resulting  filtrate  then  treated  with  potas- 
sium chloride  until  no  more  precipitation  takes  place.  The 
potassium  salt  of  the  quinone  sulphonic  acid  is  then  filtered 
off,  washed  with  cold  water,  and  recrystallised  from  alcohol. 
Yield  84  per  cent. 

PREPARATION  OF  £.-BENZOQUINONE-CHLORIMIDE 
(Cl :  N .  C6H4 : 0)  ?  Forty-five  grammes  of  sodium  hydroxide 

1  A.  183,  242. 

2  A.  189,153;   194,  202;  211,49;  B.  25,  982. 

3  B. 37, 1498- 


ALDEHYDES,  KETONES,  QUINONES  141 

are  dissolved  in  250  c.c.  of  water,  and  chlorine  passed  into  the 
solution  until  35  grm.  of  the  gas  have  been  taken  up.  The 
solution  is  then  diluted  with  ice  and  water  to  500  c.c.,  and  a 
solution  of  43  grm.  of  £.-amino-phenol  in  500  c.c.  water  and 
100  c.c.  concentrated  hydrochloric  acid  run  in  slowly.  The 
chlorimide  separates  in  yellow  flocks,  which  after  washing 
and  drying  are  recrystallised  from  petroleum  ether.  M.P.  85°. 

PREPARATION      OF      £.-BENZOQUINONE  -  DICHLORI- 

MIDE  (ClN:C6H4:NCl).i  Ninety  grammes  of  caustic  soda 
are  dissolved  in  500  c.c.  of  water,  and  chlorine  passed  into 
the  cold  solution  until  it  has  gained  75  grm.  in  weight.  It 
is  then  diluted  to  1500  c.c.  with  ice  and  water.  A  solution 
of  54  grm.  of  ^.-phenylenediamine  hydrochloride  in  600  c.c.  of 
water  and  120  c.c.  of  concentrated  hydrochloric  acid  is  then 
slowly  run  into  the  cold  solution  thus  obtained.  A  blue 
coloration  at  first  appears,  but  this  soon  vanishes,  and  snow- 
white  flocks  of  the  dichlorimide  are  precipitated.  These  are 
collected,  washed  until  the  filtrates  show  no  chlorine  reaction, 
and  finally  either  recrystallised  from  70  per  cent,  alcohol,  or 
extracted  in  a  Soxhlet  apparatus  with  petroleum  ether  of  low 
boiling-point  (ligroin,  boiling  at  120°,  should  not  be  used). 
Colourless  needles  which  explode  at  126°.  (Take  care  !) 

PREPARATION  OF  AMINO-NAPHTHOQUINONEIMIDE 
SULPHONIC  ACID. 2  i  -  Naphthol  -  2.4  -  diamino  -  7  -  sulphonic 
acid  hydrochloride  (by  the  reduction  of  Naphthol  Yellow  S, 
p.  213)  is  either  warmed  with  excess  of  ferric  chloride  dissolved 
in  dilute  hydrochloric  acid,  or  it  is  dissolved  in  ammonia  and 
a  rapid  current  of  air  then  blown  through  the  cold  solution. 
In  either  case  the  quinoneimide  separates  in  brick-red  needles 
which  only  require  to  be  collected  and  washed  with  water. 
The  yield  by  both  methods  is  about  65  per  cent.  The  formula 
of  the  substance  is  : 

O  O 

I!  II 

S08H/\/\  _  NH  S03H/\/\— NH2 


or 

\/X  ' 

NH2 
1  Loc.  cit. 


142      PREPARATION  OF  ORGANIC  COMPOUNDS 

A  similar  compound  is  obtained  by  oxidising  the  reduction 
compound  of  Martins'  Yellow:1 


OH 


OH 


NH, 


I-I 


N02 
Martius'  Yellow 

O 


O 


or 


NH2 

Amino  -naphthoquinoneimide 


NH 


DIHYDRIC  PHENOLS.  The  o.-dihydric  phenols  of 
the  benzene  series  serve  for  the  preparation  of  the 
o.-benzoquinones.2  The  oxidation  is  brought  about 
by  anhydrous  silver  oxide  in  absolute  ether.  The 
o.-benzoquinones  are,  however,  exceedingly  difficult 
to  prepare,  and  for  the  success  of  the  experiment  every 
trace  of  moisture  must  be  excluded. 

The  ^>.-dihydric  phenols  are  very  readily  oxidised  to 
the  corresponding  quinones  (FeCl3,  K2Cr2O7,  PbO2, 
&c.),  the  quinhydrones  (see  p.  103)  being  formed  as 
intermediate  products  : 


OH 


/ 


OH 

Hydroquinone 


/\ 


OH 


O 


/\ 


•OH 


Quinhydrone 


o 

Quinone 


1  A.  134,  377. 


2  B.  20,  1776  ;  37,  4744. 


ALDEHYDES,   KETONES,  QU1NONES  143 

The  method,  however,  is  not  much  employed,  as  the 
hydroquinones  are  usually  made  by  the  reduction  of 
the  quinones. 

SOME  DERIVATIVES  OF  THE  ALDEHYDES 
AND  KETONES 

The  >CO  group  in  the  aldehydes  and  ketones  is 
very  reactive  and  readily  gives  rise  to  condensation 
products,  and  some  of  these  are  of  the  greatest  impor- 
tance for  isolating,  purifying,  and  identifying  the 
aldehydes  and  ketones.  The  condensation  products 
with  ammonia  and  primary  aromatic  amines  have 
already  been  dealt  with  on  p.  108  (see  also  p.  233). 
The  very  important  addition  products  with  sodium 
bisulphite  have  been  discussed  under  benzaldehyde 
(p.  ii3),salicyl  aldehyde  (p.  120),  acetone  (p.  122),  and 
dichloracetone  (p.  123). 

OXIMES.  The  oximes  are  formed  by  the  loss  of  a 
molecule  of  water  between  one  molecule  of  hydroxyl- 
amine  and  one  molecule  of  the  ketone  or  aldehyde  : 


/ 


R  /R 


R—  C          +  H2NOH  =  R—  C  :  N.OH  +  H2O. 

^O 

The  hydroxylamine  is  applied  in  the  form  of  one 
of  its  salts  (usually  the  hydrochloride)  ,  which  may  or 
may  not  be  first  neutralised  by  the  addition  of  one 
molecule  of  a  basic  substance  such  as  caustic  soda, 
sodium  acetate,  sodium  ethylate,  or  barium  carbonate. 
This  last  is  said  to  be  especially  valuable.  Aniline 
is  also  sometimes  used,  e.g.  in  the  preparation  of  the 
oxime  of  acetoacetic  ester.1  Alcohol  is  almost  invari- 
ably used  as  a  solvent.  The  aldoximes,  as  a  rule,  are 
formed  at  the  ordinary  temperature,  whereas  the 
formation  of  ketoximes  usually  requires  the  application 
of  heat,  prolonged  heating  under  pressure  often  being 
necessary.  As  a  class  the  oximes  suffer  from  the 

i  B.  28,  2731. 


144      PREPARATION  OF  ORGANIC  COMPOUNDS 

disadvantage  of  being  liquids  or  solids  of  low  melting- 
point  which  are  difficult  to  purify. 

PREPARATION  OF  BENZOPHENONE  OXIME.*  Thirteen 
grammes  of  benzophenone  and  3  grm.  of  hydroxylamine 
hydrochloride  are  heated  on  the  water-bath  under  a  reflux 
condenser  for  one  day  with  15  c.c.  of  90  per  cent,  alcohol,  to 
which  a  trace  of  hydrochloric  acid  has  been  added.  The 
alcohol  is  then  removed  by  evaporation  and  the  residue 
recrystallised  from  very  dilute  alcohol.  Fine  silky  needles 
melting  at  140°. 

The  monoximes  of  the  a-diketones  are  identical 
with  the  fc'so-nitroso-compounds,  and  are  dealt  with  on 
p.  198. 

The  quinone  monoximes  are  identical  with  the 
nitroso-phenols,  and  are  discussed  on  p.  195. 

THE  SEMICARBAZONES.  The  semicarbazones  are 
formed  by  the  loss  of  water  between  the  aldehyde  or 
ketone  and  semicarbazide  : 

R2CO  -f  H2N.NH.CONH2  = 

R2C:N.NH.CO.NH2+H20. 

They  show  great  powers  of  crystallisation,  and  are  very 
suitable  for  identification  purposes.  For  their  pre- 
paration semicarbazide  hydrochloride  is  dissolved  in 
a  little  cold  water  and  then  neutralised  (Congo  paper) 
with  alcoholic  potassium  acetate.  The  ketone  is  then 
added,  and  the  whole  diluted  with  alcohol  and  water 
until  complete  solution  takes  place.  The  reaction, 
which  takes  place  at  the  ordinary  temperature,  requires 
from  a  few  minutes  to  several  days,  and  is  complete 
when  a  sample  poured  into  water  gives  a  hard  crys- 
talline precipitate.  Another  method  consists  in  dis- 
solving i  part  of  semicarbazide  hydrochloride  in 
3  parts  of  water  and  then  adding  i  part  of  potassium 
acetate.  Rather  less  than  the  calculated  quantity  of 
the  ketone  is  then  added,  and  the  whole  shaken 
mechanically.  The  semicarbazone  usually  begins  to 

1  B.  19,  989. 


ALDEHYDES,  KETONES,  QUINONES  145 

separate  almost  at  once,  but  should  this  not  be  the  case 
its  formation  may  be  accelerated  by  the  addition  of  a 
little  acetone  free  from  methyl  alcohol.  The  semi- 
carbazones  are  best  purified  by  recrystallisation  from 
pure  acetone. 

PREPARATION    OF    ^.-CAMPHOR     SEMICARBAZONE.i 

Twelve  grammes  of  semicarbazide  hydrochloride  and  15  grm. 
of  sodium  acetate  are  dissolved  in  20  c.c.  of  water,  and  15  grm. 
of  camphor  in  20  c.c.  of  glacial  acetic  acid  added.  The  whole 
is  gently  warmed  and  warm  glacial  acetic  acid  added  until  a 
clear  solution  is  obtained.  On  cooling,  part  of  the  semi- 
carbazone  crystallises  out  and  the  rest  is  obtained  by  precipi- 
tating with  water.  After  washing,  the  whole  is  recrystallised 
from  alcohol  or  benzene.  Colourless  needles  melting  at  236°- 
238°. 

The  thio-semicarbazones,  R2C  :N.NH.CS.NH2,  are 

obtained  in  much  the  same  way  as  the  semicarbazones. 
They  have  the  advantage  of  forming  insoluble  salts 
with  certain  heavy  metals,  especially  with  silver  : 

R2C:N.NH.C:NH 

I 
S.Ag 

THE  AMINOGUANIDINE  DERIVATIVES.  Amino- 
guanidine  combines  with  aldehydes  and  ketones  with 
loss  of  water  : 

/NHNH2  /NHN:CR2 

R2CO  +HN  :  C<  =  HN  :  C<(  +  H2O. 

XNH2  XNH2 

The  resulting  compounds  form  very  well  crystalline 
picrates. 

The  condensation  takes  place  in  the  presence  of 
mineral  acid.  In  the  aliphatic  and  terpene  series 
aminoguanidine  hydrochloride  is  dissolved  in  water 
containing  a  little  hydrochloric  acid.  The  ketone  is 
added,  and  then  alcohol  until  a  clear  solution  is  obtained. 
The  whole  is  boiled  for  a  short  time  under  a  reflux 

i  B.  28,  2192, 

10 


146      PREPARATION  OF  ORGANIC  COMPOUNDS 

condenser,  poured  into  water,  and  made  alkaline  with 
caustic  soda.  The  solution  is  then  extracted  with  ether, 
the  ether  removed  by  distillation,  and  the  residue 
suspended  in  hot  water  and  treated  with  aqueous 
picric  acid  solution.  The  picrate  is  precipitated  and  is 
recrystallised  from  strong  or  dilute  spirit  according  to 
circumstances. 

With  aromatic  aldehydes,  aminoguanidine  nitrate  is 
dissolved  in  water  and  then  shaken  up  with  the  aldehyde, 
alone  or  in  alcoholic  solution.  On  addition  of  a  few 
drops  of  nitric  acid  condensation  takes  place  almost 
at  once,  and  the  difficultly  soluble  nitrate  of  the 
aminoguanidine  derivative  is  precipitated  in  the  pure 
state.  Quinones  can  be  condensed  with  the  nitrate  in 
the  same  way,  but  in  this  case  the  whole  must  be 
boiled  for  a  few  minutes. 

THE  PHENYLHYDRAZONES,  ETC.  The  phenyl- 
hydrazones  are  formed  according  to  the  equation  : 

R2CO  +  H2N.NHPh  =  R2C  :  N .NHPh  +  H20. 

The  phenyl  hydrazine  is  applied  in  dilute  acetic 
acid  solution  (dissolve  the  free  base  in  one  volume  of 
50  per  cent,  acetic  acid  and  then  dilute  with  three 
volumes  of  water),  or  the  hydrochloride  is  dissolved  in 
8  to  10  parts  of  water  containing  excess  of  sodium 
acetate  (i j-  parts) .  The  hydrazone  usually  crystallises 
out  on  standing  at  the  ordinary  temperature.  The  pre- 
paration of  mannose  phenylhydrazone  was  described 
on  p.  in. 

The  osazones,  which  may  be  regarded  as  bis-phenyl- 
hydrazones,  were  discussed  on  p.  122. 

Instead  of  phenyl  hydrazine  itself  some  of  its  deri- 
vatives are  sometimes  employed.  Thus  as.-benzyl 
phenyl  hydrazine  : 

/CH2C6H5 


C6H5N 


NH« 


reacts    more  readily   than   phenyl    hydrazine   itself, 
and  usually  gives  more  insoluble  products.    The  con- 


ALDEHYDES,  KETONES,  QUINONES  147 

densation  is  brought  about  in  warm,  neutral,  alcoholic 
solution,the  hydrazone  being  subsequently  precipitated 
by  water.  ^.-Bromphenyl  hydrazine  is  applied  in 
dilute  acetic  acid  solution.  as.-Methyl  phenyl  hydra- 
zine, CH3(C6H5)N.NH2,  often  gives  osazones  only  from 
ketones,  and  hence  serves  for  separating  mixtures  of 
aldoses  and  ketoses.1 

/H 

The     alcoholates,      R.C^-OH,    and     the     acetals, 

XOR 

R.CH(OR)2,  may  be  regarded  as  the  ethers  of  the 
unknown  gm-dihydric  alcohols,  and  are  described  on 
p.  150. 

The  cyanhydrins,  R.CH(OH)CN,  are  the  nitriles  of 
the  a-oxyacids,  and  are  discussed  on  p.  188. 

1  B.  35,  959,  2626  ;  37,  4616;   H.  36,  233. 


CHAPTER  VI 
THE  ETHERS  AND  SULPHIDES 

WITH  the  exception  of  ethyl  ether,  the  ethers  are  not 
of  great  importance.  The  aliphatic  members  are 
obtained  by  the  action  of  concentrated  sulphuric 
acid  on  the  alcohols,  the  alkyl  sulphuric  acids  being 
formed  as  intermediate  products  : 

R.OH  +  H2SO4  =  R.O.SO3H  +  H2O 
R.O.S03H  +  HO.R  =  R2O  +  H2S04. 

Ethers  containing  two  different  radicals  are  best 
obtained  by  treating  the  sodium  alcoholate  with  the 
alkyl  halide,  preferably  the  iodide  : 

R.ONa  +  R'l  =  R.O.R'  +  Nal. 

PREPARATION  OF  DIETHYL  ETHER  (C2H6)2O.  One 
hundred  grammes  of  concentrated  sulphuric  acid  are  slowly 
added  to  an  equal  weight  of  alcohol,  the  whole  being  well 
shaken  and  cooled  during  the  process.  The  mixture  is  then 
placed  in  a  d  stilling  flask  attached  to  a  long  and  efficient 
condenser  and  provided  with  a  tap-funnel  and  thermometer, 
the  ends  of  both  of  which  must  dip  below  the  surface  of  the 
acid  mixture.  The  flask  is  then  heated  on  a  sand-bath.  When 
the  temperature  of  the  mixture  reaches  140°  ether  begins  to 
distil,  and  should  be  collected  in  a  receiver  which  is  cooled  with 
ice.  During  the  distillation  the  temperature  is  maintained 
at  140°,  and  alcohol  is  added  through  the  tap-funnel  at  the  rate 
at  which  the  ether  distils  over.  When  about  1 50  c.c.  of  alcohol 
have  been  added  the  process  is  interrupted,  and  the  distillate, 
which  contains  ether,  sulphurous  acid,  and  water,  washed 
first  with  50  c.c.  of  10  per  cent,  caustic  potash  and  then  with 
a  similar  volume  of  saturated  salt  solution.  The  ether  is  then 
driecj  \yith  calcium  chloride  and  distilled  from  the  water- 

148 


THE  ETHERS  AND  SULPHIDES  149 

bath.  It  forms  a  colourless  liquid  which  boils  at  35°,  and  is 
highly  inflammable.  As  obtained  above  it  contains  traces  of 
alcohol  and  water,  which  can  only  be  removed  by  treatment 
with  metallic  sodium  and  subsequent  distillation. 

The  phenolic  ethers,  ArOAlk,  are  usually  obtained 
by  treating  the  alkali  phenolates  with  the  alkyl 
iodide  : 

ArONa  +  Alkl  =  ArO.Alk  +  Nal. 

PREPARATION  OF  PHENETOLE  (C6H5OC2H5).  One 
equivalent  (2-3  grm.)  of  sodium  is  dissolved  in  30  c.c.  of  alcohol, 
and  one  equivalent  (9-4  grm.)  of  phenol  and  19-5  grm.  (i^  mol.) 
of  ethyl  iodide  added.  The  whole  is  then  boiled  under  a 
reflux  condenser  on  the  water-bath  until  no  longer  alkaline  to 
moist  litmus  paper  (about  2%  hours) .  The  alcohol  and  excess 
of  ethyl  iodide  are  then  removed  by  distillation  from  the 
water-bath,  and  the  residue  shaken  up  with  water  and  extracted 
with  ether.  The  ethereal  extract  is  washed  with  a  little 
dilute  caustic  potash  and  then  with  water.  It  is  finally  dried 
over  calcium  chloride  and  distilled.  After  the  ether  has  been 
removed  the  phenetole  passes  over  as  a  colourless  oily  liquid 
boiling  at  173°. 

In  some  cases,  e.g.  the  o.-  and  £. -nitre-phenols,  the 
ether  is  only  obtained  with  great  difficulty  by  the  above 
method.  In  such  cases  it  is  best  to  prepare  the  silver 
salt  of  the  phenol  and  then  treat  it  in  alcoholic  sus- 
pension with  the  alkyl  iodide. 

The  methyl  ethers  of  the  phenols  are  best  prepared 
by  means  of  dimethyl  sulphate.  The  reaction  is 
brought  about  by  dissolving  the  phenol  in  excess  of 
cold  caustic  potash  solution  (best  of  30  to  40  per  cent. 
strength)  and  then  shaking  with  a  slight  excess  (ij  mol.) 
of  dimethyl  sulphate  : 

R.ONa  +  Me2SO4  =  R.OMe  +  NaMeSO4. 

It  should  be  borne  in  mind  that  dimethyl  sulphate  is 
very  poisonous  (see  p.  183). 

The  yields  are  usually  excellent. 


150      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  ANISOLE  (C6H5OCH3).  One  molecule 
(9-4  grm.)  of  phenol  is  dissolved  in  50  c.c.  of  10  per  cent. 
caustic  soda,  and  well  shaken  with  12  c.c.  (i£  mol.)  of  dimethyl 
sulphate.  The  solution  becomes  warm,  and  the  anisole  separates 
out  as  an  oily  layer.  The  whole  is  then  boiled  under  a  reflux 
condenser  for  a  short  time  (to  destroy  excess  of  dimethyl 
sulphate),  more  caustic  being  added,  if  necessary,  in  order  to 
obtain  an  alkaline  reaction.  Finally  the  anisole  is  extracted 
with  ether,  the  extract  dried  over  calcium  chloride  and  then 
distilled.  The  anisole  passes  over  at  1 54°  and  forms  a  colourless 
oil.  The  yield  is  90  to  95  per  cent. 

The  acetals  are  to  be  regarded  as  the  ethers  of  the 
unknown  gem-dihydric  alcohols : 

/H 

R.C/       +  C2H5OH  =  R.CH(OC2H5)2  +  H2O. 

xo 

The  ketones  form  similar  compounds,  but  with 
greater  difficulty. 

Just  as  it  is  only  the  polyhalide  aldehydes,  such 
as  chloral,  which  combine  with  water  to  form 
hydrates,  e.g.  \ 

CC13CHO  +  H2O  =  CC13CH(OH)2 

Chloral  Chloral  hydrate 

it  is  only  the  polyhalide  aldehydes  which  combine  with 
one  molecule  of  alcohol  to  form  an  alcoholate  : 

CC13CHO  +  C2H5OH  =  CC13CH(OH)(OC2H5). 

The  acetals  are  obtained  by  loss  of  water  between 
the  aldehydes  and  the  alcohols,  and  the  reaction 
takes  place  most  readily  in  the  presence  of  alcoholic 
hydrochloric  acid.1 

PREPARATION  OF  DIETHYL  ACETAL  (CH3.CH(OC2H5)2). 
Eighteen  grammes  of  acetaldehyde  are  dissolved  in  80  grm.  of 
alcohol  containing  i  per  cent,  of  dry  hydrogen  chloride.  After 
standing  for  eighteen  hours  the  solution  is  diluted  with  its 
own  volume  of  water,  neutralised  with  potassium  carbonate, 
and  extracted  with  ether.  The  ethereal  extract  is  twice 

i  B.  30,  3053  ;   31,  545. 


THE  ETHERS  AND  SULPHIDES  151 

washed  with  a  little  water,  dried  over  potassium  carbonate, 
and  then  fractionated.  The  acetal  passes  over  at  102°- 
104°.  The  yield  is  about  50  per  cent. 

The  acetals  are  more  readily  obtained  from  ortho- 
formic  ester.1  In  this  case  the  aldehyde  or  ketone  and 
the  orthoformic  ester  are  dissolved  in  alcohol,  a  suitable 
catalyst,  such  as  mineral  acid,  ferric  chloride,  ammo- 
nium chloride,  &c.,  added,  and  the  whole  allowed  to 
stand  for  a  long  period  at  the  ordinary  temperature, 
or  boiled  for  some  time  according  to  circumstances. 
The  yields  are  often  almost  quantitative. 

THE  SULPHIDES 

The  sulphides  are  to  be  regarded  as  the  ethers  of  the 
mer  cap  tans,  and  are  of  but  slight  interest.  They  can 
be  obtained  by  allowing  the  halogen  compounds  to 
react  with  the  mercaptans,  and  this  method  has  lately 
become  of  some  importance  in  the  manufacture  of  the 
thioindigoid  dyes,  e.g.  : 


+  Cl.CH  :CHC1  — 

\/SH  \ 


I— S 

Thioindigo  Red 

For    further    details    the    reader  is  referred  to    the 
original  literature.2 

The  aliphatic  sulphides  are  best  prepared  by  heating 
the  potassium  alkyl  sulphates  with  potassium  sulphide 
in  aqueous  solution  : 

2KRS04  +  K2S  =  R2S  +  2K2SO4. 

1  B.  40,  3903. 

2  Friedlander,   "Fortschritte,"  vol.  viii.  469-488  ;  vol.  ix. 
494-646  ;   B.  43,  587  ;   44,  3125. 


1 52      PREPARATION  OF  ORGANIC  COMPOUNDS 

The  reaction  takes  place  readily,  and  the  yields  are 
usually  good. 

The  aromatic  sulphides  are  often  obtained  by  heating 
the  hydrocarbons  with  sulphur  with  or  without  a 
catalyst  (cf.  p.  274),  or  with  sulphur  dichloride  and 
aluminium  chloride.  Also  aromatic  nitro-haloid  com- 
pounds which  have  a  nitro-group  in  the  ortho-  or  ^ap- 
position to  the  halogen  atom  readily  give  sulphides 
on  treatment  with  sulphuretted  hydrogen. 

PREPARATION      OF      2.4.2/4/-TETRANITRODIPHENYL 

SULPHIDE,  ( (NO2)2C6H3)2S.i  One  molecule  of  2.4-dinitro-i- 
chlorobenzene  is  dissolved  in  boiling  alcohol,  rather  less 
than  two  molecules  of  strong  ammonia  added,  and  sulphuretted 
hydrogen  then  passed  through  the  boiling  liquid  until  no  more 
precipitation  takes  place.  The  sulphide  is  then  collected, 
washed  with  boiling  water,  and  recrystallised  from  glacial 
acetic  acid.  It  forms  yellow  needles  which  melt  at  197°. 
The  yield  is  almost  quantitative. 

It  is  important  that  rather  less  than  the  calculated  amount 
of  ammonia  should  be  used,  as  otherwise  the  nitro-groups  will 
be  attacked  : 

2(N02)2C6H3C1  +  H2S  +  2NH3  =  ((NO2)2C6H3)2S    +  2NH4C1. 
i  A.  197, 77. 


CHAPTER  VII 

THE  CARBOXYLIC  ACIDS,  THEIR  ESTERS 
AND  ANHYDRIDES 

THE  CARBOXYLIC  ACIDS 

i.  BY  THE  HYDROLYSIS  OF  THE  NITRILE, 
ACID  CHLORIDE  OR  ACID  AMIDE 

ON  hydrolysis  the  nitriles  pass  first  into  the  acid 
amide  and  then  into  the  acid  : 

R.C  :  N    —    R.CO.NH2    —    R.CO.OH 

The  first  stage  is  usually  lost  as  the  amides  are 
more  readily  hydrolysed  than  the  nitriles.  The  amide, 
however,  can  be  isolated  by  the  alkaline  peroxide 
method  described  on  p.  224. 

For  the  complete  hydrolysis  of  the  nitrile  it  is 
boiled  with  acids,  or,  better,  with  caustic  alkali  solution. 
Obstinate  cases  may  require  heating  under  pressure, 
treatment  with  mineral  acids  in  glacial  acetic  acid 
solution,  or  treatment  with  alcoholic  alkali.  In  some 
cases  where  the  hindering  influence  of  substituent 
groups  is  very  marked,  a  fusion  with  caustic  potash  is 
necessary. 

HYDROLYSIS  OF  BENZONITRILE  (C6H5CN).  Ten 
grammes  of  benzonitrile  are  boiled  with  150  c.c.  of  20  per  cent. 
caustic  potash  solution  until  no  more  ammonia  is  evolved. 
The  solution  is  cooled,  somewhat  diluted,  and  then  acidified 
with  hydrochloric  acid.  The  benzoic  acid  is  filtered  off, 
washed  with  cold  water,  and  recrystallised  from  boiling  water. 
The  yield  is  almost  quantitative.  Colourless  leaflets  melting 
at  120°. 


i54      PREPARATION  OF  ORGANIC  COMPOUNDS 

HYDROLYSIS      OF      a-NAPHTHONITRILE     (C10H7CN).i 

Twelve  grammes  of  a-naphthonitrile,  7-5  grm.  of  caustic  soda, 
and  55  c.c.  of  alcohol  are  heated  in  a  sealed  tube  to  160°  for 
six  hours.  After  cooling,  the  contents  of  the  tube  are  well 
diluted  with  water  and  then  acidified  with  hydrochloric  acid. 
The  naphthoic  acid  is  filtered  off,  washed  with  water,  and  re- 
crystallised  from  alcohol.  Colourless  crystals  melting  at 
160°.  The  yield  is  almost  quantitative. 

The  hydrolysis  can  also  be  brought  about  by  heating  in  an 
op'en  vessel  with  a  solution  of  concentrated  sulphuric  acid  in 
glacial  acetic  acid. 

It  is  often  unnecessary  to  isolate  the  pure  nitrile,  it 
being  in  many  cases  sufficient  to  hydrolyse  the  crude 
substance  obtained  by  the  action  of  potassium  cyanide 
on  alkyl  halides.  If  the  hydrolysis  is  carried  out  with 
a  mixture  of  alcohol  and  concentrated  sulphuric  acid, 
simultaneous  esterification  takes  place  (cf.  p.  177). 

PREPARATION     OF     DIETHYL     MALONATE 

(CH2(CO2C2H6)2).  Fifty  grammes  of  chloracetic  acid  are 
dissolved  in  100  c.c.  of  water  at  5o°-6o°,  and  the  solution 
neutralised  in  a  large  basin  with  sodium  carbonate  (about 
45  grm.  of  the  anhydrous  salt) .  When  no  more  carbon  dioxide 
is  evolved,  40  grm.  of  potassium  cyanide  in  small  lumps  are 
added  slowly.  When  the  brisk  reaction  is  over,  the  solution 
is  evaporated  as  rapidly  as  possible  in  a  fume  chamber. 
During  the  evaporation  the  whole  must  be  continually  stirred. 
The  evaporation  is  continued  until  the  temperature  reaches 
135°.  Without  interrupting  the  stirring  the  mass  is  rapidly 
cooled,  coarsely  ground,  mixed  with  20  c.c.  of  alcohol,  and 
transferred  to  a  flask  fitted  with  a  reflux  condenser.  A  well- 
cooled  mixture  of  80  c.c.  of  alcohol  and  80  c.c.  of  concentrated 
sulphuric  acid  is  then  run  in  during  fifteen  minutes,  and 
the  whole  heated  on  the  water-bath  for  one  or  two  hours. 
After  cooling,  100  c.c.  of  water  are  added,  and  the  whole  filtered. 
The  residue  is  washed  several  times  with  ether,  the  filtrate 
repeatedly  extracted  with  ether,  and  the  ethereal  extracts 
washed  with  sodium  carbonate  solution  until  no  longer  acid. 
The  ethereal  solution  is  dried  with  calcium  chloride,  and  the 
ether  then  removed  by  distillation  from  the  water-bath. 

1  B.  20,  241. 


THE  CARBOXYLIC  ACIDS  155 

The  residual  oil  is  distilled  under  reduced  pressure.     It  forms 
a  colourless  liquid  boiling  at  195°. 

Acid  chlorides  are  usually  saponified  by  water.  The 
aromatic  acid  chlorides,  however,  are  but  slowly 
attacked,  and  are  best  heated  with  dilute  (10  per  cent.) 
caustic  soda  solution. 

The  acid  amides  are  best  boiled  with  10  per  cent. 
caustic  alkali  solution  until  no  more  ammonia,,  is 
evolved. 

2.  BY  THE  OXIDATION  OF  THE  ALCOHOLS, 
ALDEHYDES,  AND  KETONES 

The  primary  alcohols  on  oxidation  pass  first  into 
the  corresponding  aldehyde  (p.  109)  and  then  into  an 
acid  containing  the  same  number  of  carbon  atoms  as 
the  alcohol : 

R.CH2OH     r*     R.CHO  R.COOH. 

The  secondary  alcohols  on  oxidation  first  give  a 
ketone,  and  then  an  acid  with  fewer  carbon  atoms 
than  the  alcohol : 

/CH3  /CH3  .OH 

R.C/H          —       R.C/  —        R.C/      +C02+HoO. 

\OH  X0  ^O 

The  tertiary  alcohols  on  oxidation  undergo  complete 
decomposition. 

The  oxidation  of  the  aliphatic  alcohols  is  best  carried 
out  with  chromic  acid  mixture,  whereas  in  the  aromatic 
series  permanganate  is  the  best  oxidising  agent.  In 
all  cases  esters  and  acetals  usually  appear  as  side- 
products. 

Polyhydric  aliphatic  alcohols  are  oxidised  with  nitric 
acid,  but  complete  disruption  of  the  molecule  often 
takes  place. 

PREPARATION  OF  SACCHARIC  ACID  (COOH(CHOH)4 
COOH).  Fifty  grammes  of  glucose  are  heated  on  the  water- 
bath  with  300  c.c.  nitric  acid  (D  =  1-15),  and  the  solution 


156     PREPARATION  OF  ORGANIC  COMPOUNDS 

then  concentrated  to  a  syrup.  This  is  dissolved  in  a  little 
water  and  again  evaporated  until  a  brown  coloration  makes 
its  appearance.  The  residue  is  then  taken  up  in  150  c.c.  of 
water,  neutralised  with  potassium  carbonate,  and  evapo- 
rated until  the  volume  is  about  80  c.c.  By  frequently  scratch- 
ing the  sides  of  the  vessel  the  acid  potassium  salt  slowly 
separates  out  as  a  crystalline  mass. 

CH2OH .  (CHOH)4 .  CHO     —    COOH .  (CHOH)4  .COOH. 

PREPARATION  OF  OXALIC  ACID  (COOH)2.  One 
hundred  and  forty  grammes  of  nitric  acid  (D  —  1-32)  are 
placed  in  a  large  flask  together  with  a  trace  of  vanadium 
oxide.  The  whole  is  warmed  on  the  water -bath  to  about  50°, 
and  then  20  grm.  of  finely  powdered  cane-sugar  added.  As 
soon  as  a  brisk  reaction  sets  in  with  a  copious  evolution  of  red 
fumes,  the  flask  is  set  to  stand  in  cold  water  for  at  least  twenty- 
four  hours.  The  oxalic  acid  is  then  filtered  off  and  recrystal- 
lised  from  a  small  quantity  of  boiling  water. 

PREPARATION  OF  FORMIC  ACID  (H.COOH).*  Fifty 
grammes  of  glycerine  are  dehydrated  by  cautiously  warming 
in  a  basin  until  the  temperature  reaches  175°.  It  is  then 
transferred  to  a  retort  fitted  with  a  condenser,  50  grm.  of 
oxalic  acid  added,  and  the  whole  heated.  The  reaction  sets 
in  at  about  90°,  and  the  contents  of  the  retort  are  maintained 
at  io5°-uo°  until  the  reaction  slackens.  The  whole  is 
then  allowed  to  cool  somewhat,  another  50  grm.  of  oxalic 
acid  added,  and  the  whole  again  heated.  This  process  is 
repeated  until  200  grm.  of  oxalic  acid  have  been  used.  The 
distillate,  which  consists  of  aqueous  formic  acid,  is  set  on 
one  side  and  the  contents  of  the  retort  transferred  to  a  large 
flask  and  distilled  in  steam  until  the  distillate  is  only  faintly 
acid.  The  united  distillates  are  neutralised  with  lead  carbo- 
nate, boiled  for  a  few  minutes,  and  then  filtered  from  excess  of 
lead  carbonate,  the  residue  being  well  washed  with  boiling 
water.  The  clear  filtrates  are  then  concentrated  until  crystal- 
lisation sets  in.  The  lead  formate  separates  on  cooling  in  long 
colourless  needles.  These  are  filtered  off,  washed  with  a  little 
cold  water,  and  dried.  In  order  to  obtain  the  free  acid,  the 

1  Formic  acid  is  prepared  technically  by  passing  CO  over 

JQ 
soda-lime  at  230°  :  CO  +  NaOH  «=  H.C^-ONa. 


THE  CARBOXYLIC  ACIDS  157 

powdered  lead  salt  is  loosely  packed  into  a  wide  glass  tube  held 
in  a  sloping  position  and  loosely  plugged  at  the  lower  end  with 
glass-wool  or  asbestos.  The  end  of  the  tube  is  attached  to 
a  distilling  flask  provided  with  a  calcium  chloride  tube. 
A  fairly  slow  stream  of  dry  hydrogen  sulphide  is  then 
passed  through  the  tube,  the  latter  being  gently  warmed  by 
means  of  a  burner.  The  lead  formate  blackens  owing  to  the 
formation  of  lead  sulphide,  and  the  formic  acid  collects  in  the 
distilling  flask.  When  no  more  acid  can  be  obtained,  the 
flask  is  removed,  some  lead  formate  added  (to  remove  sulphu- 
retted hydrogen),  and  the  formic  acid  distilled  off.  Colourless 
liquid  with  a  biting  smell.  B.P.  100°. 

When  a  ketone  of  the  type  R.CH2.CO.CH2.R'  is 
oxidised,  acids  R.COOH  and  R'CH2COOH  are  ob- 
tained, where  the  chain  represented  by  R'  is  longer 
than  that  represented  by  R.  Chromic  acid  is  the  best 
oxidising  agent,  but  the  method  is  of  very  minor 
importance. 

The  aldehydes  are  very  readily  converted  into  the 
corresponding  acids  by  most  oxidising  agents.  Even 
exposure  to  the  air  often  brings  about  the  change. 
Thus  benzaldehyde  rapidly  absorbs  oxygen,  giving 
benzoic  acid. 

3.  BY  THE  OXIDATION  OF  ALKYL  GROUPS 

This  method  is  limited  to  the  aromatic  series.  When 
any  aromatic  compound  containing  a  side -chain  is 
vigorously  oxidised,  the  whole  of  the  side-chain  is 
burnt  to  — COOH,  and  a  carboxylic  acid  results,  in 
which  the  carboxyl  group  is  directly  attached  to  the 
ring.  As  oxidising  agents  chromic  acid,  permanganate, 
dilute  nitric  acid,  and  potassium  ferricyanide  are 
usually  chosen. 

When  there  are  two  side-chains  present,  both  are 
oxidised  by  potassium  permanganate  and  only  one  by 
dilute  nitric  acid.  If  the  two  chains  are  in  the  meta- 
or  para-  position  to  each  other  they  are  both  oxidised 
by  chromic  acid,  but  if  in  the  ortho-  position  are  either 
unattacked  or  the  ring  is  completely  ruptured.  As  a 


158      PREPARATION  OF  ORGANIC  COMPOUNDS 

rule,   negative   groups   in   the   ortho-  position    hinder 
oxidation  with  chromic  acid. 

Potassium  ferricyanide  only  oxidises  methyl  to  car- 
boxyl  when  there  is  a  nitro-group  in  the  ortho-  position. 
Oxidation  is  facilitated  by  substituting  the  hydrogen 
in  the  side-chain  by  halogen.  If  the  side-chain  is  a 
methyl  group  and  all  three  hydrogen  atoms  are 
replaced  by  chlorine,  it  is  only  necessary  to  heat 
the  compound  with  alkalis  or  with  water  under 
pressure  : 


Ph.CCl3     -»     [PhC(OH)3]     -»     PhC          +  H20. 

\OH 

This  is  the  technical  preparation  of  benzoic  acid. 
Halogen  atoms  in  the  nucleus,  however,  hinder  oxida- 
tion, and  highly  halogenated  compounds  can  only  be 
oxidised  by  the  combined  action  of  fuming  nitric  acid 
and  potassium  permanganate. 

If  the  side-chains  form  part  of  a  ring,  as  e.g.  in 
naphthalene,  the  or^o-dicarboxylic  acid  can  be  ob- 
tained by  heating  with  sulphuric  acid  and  a  trace  of 
mercury  sulphate.  This  is  the  technical  preparation 
of  phthalic  acid  : 


9H2SO 


V— COOH 


+  2CO2+ioH2O+9SO2 


the  sulphur  dioxide  being  reconverted  into  sulphuric 
acid  by  the  contact-process. 

If  in  addition  to  the  side-chain  to  be  oxidised,  the 
molecule  contains  amino-  or  hydroxyl  groups,  these 
must  first  be  protected.  The  amino-group  can  be 
acetylated  or  benzoylated,  and  the  phenolic  group 
treated  in  the  same  way,  or  an  ester  of  sulphuric  or 
phosphoric  acid  formed.  Phenolic  groups  can  also  be 
protected  by  converting  them  into  methoxy-groups 
by  means  of  dimethyl  sulphate.  This  method  has 
the  disadvantage  that  the  methyl  groups  are  trouble- 
some to  remove  when  the  oxidation  has  been  com- 


THE  CARBOXYLIC  ACIDS  159 

pleted.  The  protected  amino-compoimds  are  oxidised 
with  neutral  potassium  permanganate,  i.e.  potassium 
permanganate  in  the  presence  of  excess  of  magnesium 
sulphate  : 

2KMnO4  +  H2O  =  2KOH  +  2MnO2  +  30. 
2KOH  +  MgS04  =  Mg(OH)2  +  K2SO4. 

The  protected  phenols  are  oxidised  with  alkaline 
potassium  permanganate. 

The  protecting  groups  are  subsequently  removed  by 
hydrolysis. 

PREPARATION  OF  BENZOIC  ACID  (C6H5COOH). 
Thirteen  grammes  of  benzyl  chloride  and  n  grm.  of  sodium 
carbonate  are  heated  under  a  reflux  condenser,  and  a  solution  of 
22  grm.  potassium  permanganate  in  about  half  a  litre  of  water 
is  slowly  run  in.  The  boiling  is  continued  until  the  colour  of 
the  permanganate  has  completely,  or  almost  completely, 
vanished.  The  liquid  is  then  cooled  and  treated  with  sulphur 
dioxide  gas  until  the  precipitated  manganese  hydroxide 
has  redissolved.  The  benzoic  acid  is  filtered  from  the  cold 
solution,  washed  with  cold  water,  and  recrystallised  from 
boiling  water.  Colourless  needles  melting  at  121°.  The  yield 
is  almost  theoretical. 


PREPARATION    OF    PHTHALIC   ACID,i       64 

[2  JLAJUJtl. 

Twenty  grammes  of  naphthalene,  10  grm.  of  mercuric  sulphate, 
and  300  grm.  of  concentrated  sulphuric  acid  (monohydrate) 
are  placed  in  a  retort  which  is  clamped  with  the  neck  in  an 
upright  position.  The  whole  is  warmed  until  the  naphthalene 
has  gone  into  solution.  The  retort  is  then  lowered  to  a  normal 
position,  an  air  condenser  sealed  or  luted  with  plaster  of  Paris 
on  to  the  end,  and  the  retort  heated  strongly.  The  reaction 
commences  at  2OO°-25o°  and  becomes  vigorous  at  300°, 
a  mixture  of  phthalic  acid  with  some  sulphophthalic  acid 
and  unchanged  naphthalene  passing  over,  together  with  the 
carbon  dioxide,  sulphur  dioxide,  and  water.  The  distillate  is 
collected  in  about  250  c.c.  of  cold  water,  and  the  distillation 
continued  until  the  mass  in  the  retort  is  nearly  dry.  The 
distillate  is  filtered  and  the  precipitate  washed  with  cold  water 

1  D.R.P.  91,202. 


160      PREPARATION  OF  ORGANIC  COMPOUNDS 

and  then  dissolved  in  caustic  soda.  Unchanged  naphthalene 
is  removed  by  nitration,  and  the  phthalic  acid  then  repreci- 
pitated  with  hydrochloric  acid.  It  is  finally  purified  by  re- 
crystallisation  from  hot  water  or  aqueous  alcohol.  It  forms 
colourless  plates,  and  on  heating  passes  into  the  anhydride, 

/C0\ 
C6H4<^         /O.     This  latter  sublimes  in  long  needles  melting 

Nxx 

at  128°.     The  yield  is  about  70  per  cent. 


PREPARATION  OF  £.-OXYBENZOIC  ACID  (C6H4[i]OH 
[4JCOOH).1  £.-Cresol  is  converted  into  potassium-/?.  -cresyl 
sulphate  by  treating  its  concentrated  solution  at  6o°-7O° 
with  potassium  pyrosulphate  (ij  parts)  for  eight  to  ten  hours. 
The  potassium  salt  is  then  dissolved  by  warming  with  an 
equal  weight  of  potassium  hydroxide  dissolved  in  a  little 
water.  The  solution  is  heated  on  the  water-bath,  and  rather 
more  than  the  calculated  quantity  (one  molecule)  of  potassium 
permanganate  in  4  per  cent,  solution  slowly  added,  and  the 
whole  heated  for  some  hours.  Excess  of  permanganate  is 
then  destroyed  by  adding  a  few  drops  of  alcohol  and  continuing 
the  heating  until  a  filtered  sample  no  longer  shows  a  pink 
colour.  The  whole  is  filtered  hot,  the  filtrate  acidified 
with  hydrochloric  acid,  and  then  warmed  on  the  water-bath 
to  hydrolyse  the  sulphuric  ester.  On  cooling,  the  greater 
part  of  the  acid  crystallises  out  and  the  rest  is  extracted  with 
ether.  After  recrystallisation  from  water  it  melts  at  210°. 
The  yield  is  almcst  theoretical. 

PREPARATION  OF  ANTHRANILIC  ACID  (C6H4[i]NH2 
[2JCOOH).2  Five  parts  of  acet-o.-toluide,  10-3  parts  of 
crystallised  magnesium  sulphate,  and  600  parts  of  water  are 
heated  to  75°-8o°.  At  this  temperature  14-6  parts  of  solid 
potassium  permanganate  are  added,  and  the  whole  heated  to 
85°  for  i£  hours.  The  liquid  is  filtered  hot,  and  the  filtrate 
on  cooling  acidified  with  dilute  sulphuric  acid,  when  acet- 
anthranilic  acid  is  precipitated.  M.P.  185°.  The  acetyl  group 
can  be  split  off  by  boiling  with  dilute  caustic  alkali,  or  better, 
with  dilute  hydrochloric  acid.  Anthranilic  acid  itself  melts 
at  145°. 

i  B.  19,  705.  2  D.R.P.  94,629 


THE  CARBOXYLIC  ACIDS  161 

4.     FROM   THE   ALKYL   MAGNESIUM 
COMPOUNDS 

When  an  alkyl  or  aryl  halide,  preferably  the  iodide,  is 
treated  in  absolute  ethereal  solution  with  clean  magne- 
sium ribbon,  an  alkyl  or  aryl  magnesium  compound 
is  obtained  : 


R.Hlg  +  Mg  =  Mg 


XHlg 
This  on  treatment  with  CO2  forms  a  carboxylic  acid  : 

/O—  MgHlg 
R_Mg—  Hlg  +  C02  -  R.C/ 

^o 

,0.  MgHlg  ,OH 

R.C/          +H20  =  R.C^         +Mg(OH)Hlg. 


The  formation  of  the  alkyl  or  aryl  magnesium 
halide  is  often  facilitated  by  the  addition  of  a  trace  of 
iodine,  or  by  first  heating  the  magnesium  in  iodine 
vapour.1  Tertiary  bases,  such  as  dimethyl  aniline,  also 
act  as  catalysts. 

PREPARATION  OF  BENZOIC  ACID  (PhCOOH).2  The 
ether  used  in  this  experiment  must  be  dried  by  distillation 
over  metallic  sodium  or  phosphorus  pentoxide,  and  all  vessels 
must  be  scrupulously  dry.  Forty  cubic  centimetres  of  absolute 
ether,  2-4  grm.  of  clean  magnesium  ribbon,  20-4  grm.  of 
iodobenzene,  and  a  trace  of  iodine  are  heated  under  a  reflux 
condenser  until  the  reaction  sets  in  and  the  liquid  remains 
in  ebullition  when  the  water-bath  is  removed.  When  the 
reaction  begins  to  slacken,  the  water-bath  is  replaced,  and  the 
boiling  continued  until  all  the  magnesium  has  dissolved  (about 
half  an  hour).  The  solution  is  then  cooled  in  melting  ice, 
and  treated  at  this  temperature  with  a  moderately  rapid 
stream  of  dry  carbon  dioxide  for  three  hours.  The  solution 
is  then  decomposed  by  adding  ice,  acidified  with  15  c.c.  of 

i  B.  38,  2759,  2  B.  35   2519. 

ii 


162      PREPARATION  OF  ORGANIC  COMPOUNDS 

concentrated  hydrochloric  acid,  diluted  with  its  own  volume 
of  water,  and  the  benzoic  acid  shaken  out  with  ether.  The 
ethereal  solution  is  extracted  with  dilute  caustic  soda,  and  the 
benzoic  acid  precipitated  from  the  alkaline  extract  by  acidifying 
with  hydrochloric  acid.  The  acid  is  purified  by  recrystallisa- 
tion  from  water.  It  melts  at  121°.  The  yield  is  90  to  95  per 
cent. 

Instead  of  using  carbon  dioxide,  chloroformic  ester 
or  a  carbonic  ester  may  be  used,  in  both  of  which 
cases  the  ester  and  not  the  free  acid  is  obtained  : 

R.Mg.Hlg  +  Cl.COOEt  =  R.COOEt  +  MgHlgCl 

EtOx  /Hlg 

R.MgHlg  +  )CO  =  R.COOEt  +  Mg/ 

EtO/ 


5.  BY  THE  FRIEDEL-CRAFT'S  REACTION 

Under  the  influence  of  aluminium  chloride  aromatic 
compounds  condense  with  urea  chloride,  C1.CO.NH2, 
to  give  acid  amides,  with  chloroformic  ester  to  give 
carboxylic  esters,  and  with  phosgene  to  give  acid 
chlorides.  In  the  last  case,  however,  the  chief 
product  is  usually  the  ketone  (cf.  p.  127).  The  halogen 
acids,  such  as  chloracetic  acid,  can  also  be  made  to 
condense.  The  condensation  is  usually  carried  out  by 
dissolving  the  aromatic  compound  in  about  3  parts  of 
dry  carbon  bisulphide.  The  halogen  compound  (one 
molecule)  is  added,  and  then  an  equal  weight  of 
powdered  anhydrous  aluminium  chloride  in  small 
quantities  at  a  time.  When  the  reaction  has  moderated, 
the  whole  is  warmed  for  a  short  time  on  the  water- 
bath,  the  carbon  bisulphide  poured  off,  and  the  pasty 
residue  decomposed  with  ice. 

6.  BY  KOLBE'S  METHOD 

This  method  is  limited  to  the  preparation  of  phenolic 
acids,  and  consists  in  treating  the  dry  sodium  phenolate 
with  carbon  dioxide.  The  carboxyl  group  enters  the 
ovilio-  position  to  the  phenolic  group,  but  if  the  potassium 


THE  CARBOXYLIC  ACIDS  163 

phenolate  is  used  the  carboxyl  group  often  takes  the 
Para-  position  : 

C6H5ONa  +  CO2  =  C6H5.O.COONa. 

C6H5O.COONa  +  C6H5ONa  = 

[i]OH 

+  C6H5OH. 


On  the  manufacturing  scale  the  reaction  is  carried 
out  under  pressure,  the  whole  of  the  phenolate  being 
converted  into  the  carboxylic  acid  : 

C6H5O.COONa  =  C6H5(OH)COONa. 

The  reaction  takes  place  most  easily  with  polyhydric 
phenols,  heating  under  pressure  with  aqueous  solutions 
of  potassium  bicarbonate  often  being  sufficient.1 

PREPARATION    OF    SALICYLIC    ACID,    Q^ 

Thirty  grammes  of  phenol  are  gradually  added  to  a  solution 
of  12-5  grm.  of  caustic  soda  in  20  c.c.  of  water.  The  solution 
is  cautiously  evaporated  in  a  basin  until,  on  cooling,  it  can  be 
readily  powdered.  This  powdering  should  be  done  as  rapidly 
as  possible,  and  the  powdered  sodium  compound  at  once 
transferred  to  a  tubulated  retort.  The  powder  is  then  com- 
pletely dried  by  heating  in  an  oil-bath  to  140°  in  a  fairly  rapid 
stream  of  dry  hydrogen.  When  no  more  moisture  condenses 
in  the  neck  of  the  retort  (about  one  hour)  the  temperature  is 
allowed  to  fall,  without  interrupting  the  current  of  hydrogen. 
When  fairly  cool  the  sodium  phenolate  is  again  powdered  as 
rapidly  as  possible,  replaced  in  the  retort,  and  the  temperature 
raised  to  110°,  a  rapid  stream  of  dry  carbon  dioxide  being 
passed  through  the  apparatus.  After  an  hour  the  temperature 
is  gradually  raised  so  that  in  four  hours  it  has  reached  190°, 
and  at  the  end  of  six  hours  200°.  The  temperature  is  main- 
tained at  this  point  for  one  hour.  During  the  whole  of  the 
above  process  the  retort  must  be  shaken  from  time  to  time  in 
order  to  expose  fresh  surfaces  to  the  action  of  the  gas.  After 
cooling,  the  dark-coloured  mass  is  shaken  out  of  the  retort 
without  dislodging  the  phenol  which  has  condensed  in  the  neck, 
Should  any  of  the  sodium  salicylate  have  adhered  to  the 

i  M.  i,  236,  468  ;  2,  448,  458.  2  J-  pr.  [2]  10,  95. 


1 64      PREPARATION  OF  ORGANIC  COMPOUNDS 

sides  of  the  retort  it  is  dissolved  out  with  warm  water.  The 
whole  is  boiled  up  with  water,  filtered  if  necessary,  and  the 
filtrate,  after  cooling,  acidified  with  hydrochloric  acid.  The 
crude,  dark-coloured  acid  is  filtered  off,  washed  with  cold 
water,  boiled  with  animal  charcoal  and  water,  and  filtered. 
The  acid  separates  from  the  filtrate  on  cooling  in  colourless 
needles  melting  at  155°.  The  yield  is  about  20  per  cent., 
calculated  on  the  first  equations  given  on  p.  163. 

A  variation  of  Kolbe's  method  consists  in  heating 
the  potassium  phenolate  with  carbon  tetrachloride 
under  pressure  with  sufficient  alcohol  to  give  a  clear 
solution.  Cf.  p.  120. 

7.  FROM   THE   ALDEHYDES   AND   KETONES    BY 
CONDENSATION  REACTIONS 

(a)  PERKIN'S  METHOD.  This  reaction  serves  for 
the  preparation  of  aromatic  unsaturated  carboxylic 
acids,  e.g.  cinnamic  acid,  and  is  of  very  general  appli- 
cation. The  condensation  takes  place  between  aro- 
matic aldehydes  in  which  the  aldehydic  group  is  directly 
attached  to  the  nucleus,  and  the  sodium  salts  of  ali- 
phatic acids  which  contain  the  group  — CH2COOH, 
the  anhydride  of  the  acid,  or  acetic  anhydride  being 
used  as  a  condensing  agent.  It  is  best  when  possible 
to  use  the  anhydride  of  the  acid  the  sodium  salt  of 
which  is  undergoing  condensation,  as  if  acetic  anhydride 
is  used  there  is  a  risk  of  double  decomposition  : 

(CH3CO)2O  +  2CH3.CH2.CH2COONa  =  2CH3COONa  + 
(CH3.CH2.CH2CO)20 

leading,  of  course,  to  a  mixture  of  condensation 
products.  Cf.  p.  174. 

The  reaction  can  be  considered  to  take  place  in  two 
steps,  viz.  : 

(i)  An  a-hydrogen  atom  from  the  fatty  acid  salt 
attaches  itself  to  the  aldehydic  oxygen  atom  : 

/K   /R 

Ar,CHO  t  R,CH?.COOH  =  Ar.C^ C^-COONa. 

\OH\H 


THE  CARBOXYLIC  ACIDS  165 

(ii)  Water  is  split  out  with  the  formation  of  a  double 
bond  : 

/H  /R  v/R 

Ar.C(-  -  C^-COONa  =  Ar.CH  :  C\ 

^  XCOONa 


It  should  be  noticed  that  it  is  always  the  a-carbon 
atom  which  becomes  attached  to  the  aldehydic  group. 
The  reaction  takes  place  best  at  a  temperature  of  about 
180°.  If  the  aldehyde  contains  a  phenolic  group  in 
the  ortho-  position  to  the  aldehydic  group,  a  further 
loss  of  water  takes  place  with  the  formation  of  a 
lactone  : 


CH3C02Na 


CH  f    X,CH  =CH 


—  C 


/\          90  'x      '-0-CO 

X0(HOHj 
Salicylic  aldehyde  Coumaric  acid  Coumarin 

PREPARATION  OFCINNAMIC  ACID  (C6H5CH :  CHCOOH)  .1 
Thirty  grammes  of  freshly  distilled  acetic  anhydride,  20  grm.  of 
freshly  distilled  benzaldehyde,  and  10  grm.  of  powdered, 
freshly  prepared,  anhydrous  sodium  acetate  are  heated  under  a 
reflux  condenser  on  the  oil-bath  to  180°  for  ten  to  fifteen  hours. 
It  is  advantageous  to  provide  the  top  of  the  condenser  with  a 
calcium  chloride  tube.  The  product  is  rendered  alkaline 
with  sodium  carbonate,  and  any  unchanged  benzaldehyde 
removed  by  distillation  in  steam.  The  liquid  is  then  filtered 
hot,  cooled,  and  acidified  with  hydrochloric  acid.  The 
cinnamic  acid  is  filtered  off,  washed  with  a  little  cold  water, 
and  then  recrystallised  from  boiling  water.  Colourless  prisms 
melting  at  133°.  The  yield  is  about  15  grm. 

When  sodium  succinate  is  employed  in  Perkin's 
condensation,  the  first  step  of  the  reaction  takes  place 
with  great  ease  : 

/H      CH2.COONa  /H      /COONa 

C6H5C<T      +    |  -  C6H5— C^ — C^CH2.COONa. 

X0       CH2 .  COONa  X)H  \H 

1  A.   100,  126  ;   Soc.  21,  53  ;   B.  10,  68  ;   14,  1826. 


166     PREPARATION  OF  ORGANIC  COMPOUNDS 

Here,  however,  a  y-oxy-acid  is  formed,  and  the  second 
stage  of  the  reaction  consists  in  lac  tone  formation,  a 
paraconic  acid  being  the  final  product  : 

Ph.CH CHCOOH          Ph.CH— CH.COOH 


fio     — *•  Orj2 

I    :  /  ' 

OH  / 

i    HO.  ICO  °-CO 

Phenyl  paraconic  acid 

PREPARATION      OF      PHENYL      PARACONIC      ACID.1 

Nineteen  grammes  of  freshly  distilled  benzaldehyde,  21  grm. 
of  acetic  anhydride,  and  32  grm.  of  sodium  succinate  are  heated 
to  1 00°  for  fifteen  to  twenty  hours.  The  product  is  freed 
from  excess  of  benzaldehyde  by  distillation  in  steam,  and 
then  dissolved  as  far  as  possible  in  boiling  water.  After  cooling, 
the  clear  filtrate  is  acidified  with  hydrochloric  acid  and  then 
extracted  with  ether.  The  ethereal  extract  is  thoroughly 
extracted  with  sodium  carbonate  solution,  and  the  alkaline 
liquid  warmed  on  the  water-bath  to  remove  dissolved  ether. 
On  acidifying  with  hydrochloric  acid,  a  mixture  of  phenyl- 
iso-cro tonic  acid  and  phenyl  paraconic  acid  is  precipitated. 
The  precipitate  is  washed  with  cold  water,  dried,  and  extracted 
with  carbon  bisulphide,  in  which  phenyl  paraconic  acid  is 
quite  insoluble.  It  is  recrystallised  from  water  and  forms 
colourless  needles  which  melt  at  99°.  The  phenyl-zso-crotonic 
acid  is  obtained  from  the  carbon  bisulphide  by  distilling  off 
the  solvent,  and  then  recrystallising  the  residue  from  water. 
It  forms  colourless  needles  which  melt  at  86°. 

In  the  case  of  malonic  acid  the  reaction  takes  place 
with  even  greater  ease. 

PREPARATION  OF  BENZALMALONIC  ACID  (C6H6CH  : 
C(COOH)2).2  Fifteen  grammes  of  malonic  acid,  15  grm.  of 
benzaldehyde,  and  8  grm.  of  glacial  acetic  acid  are  heated  to 
100°  for  eight  to  ten  hours.  On  cooling,  the  benzalmalonic 
acid  crystallises  out,  and  in  order  to  purify  it,  it  is  merely 
necessary  to  wash  it  with  chloroform.  It  melts  at  I95°-I96° 
with  decomposition.  Yield  12  grm. 

1  A.  216,  99  ;    256,  63.  2  A.  218,  129. 


THE  CARBOXYLIC  ACIDS  167 

Condensation  between  sodium  malonate,  benzaldehyde,  and 
acetic  anhydride  takes  place  at  the  ordinary  temperature,1  but 
the  above  method  gives  better  yields. 

As  the  malonic  acids  readily  lose  carbon  dioxide  on 
heating,  the  above  method  can  be  used  for  the  pre- 
paration of  monobasic  acids.  Thus  benzalmalonic 
acid,  when  heated  to  20O°-2io°  until  no  more  carbon 
dioxide  is  evolved,  leaves  cinnamic  acid  : 

/COOH 

C6H5CH  :  C<;  —     Ph.CH  =  CH.COOH  +  CO2. 

\iCO  6|H 

A  simultaneous  condensation  and  splitting  off  of 
carbon  dioxide  occurs  when  the  aromatic  aldehydes 
are  heated  on  the  water-bath  with  one  molecule  of 
malonic  acid  and  two  molecules  of  8  per  cent,  alcoholic 
ammonia. 

PREPARATION     OF     CINNAMIC     ACID     (Ph.CH:CH. 

COOH).2  Eleven  grammes  of  benzaldehyde,  10  grm.  of  malonic 
acid,  and  3-4  grm.  of  ammonia  in  8  per  cent,  alcoholic  solution 
are  heated  on  the  water-bath  until  a  clear  solution  is  obtained. 
The  alcohol  is  then  distilled  off  and  the  residue  heated  on  the 
water-bath  until  no  more  carbon  dioxide  is  evolved.  The 
product  is  dissolved  in  hot  water  and  the  cinnamic  acid 
precipitated  with  hydrochloric  acid.  Yield  80  to  85  per  cent. 
M.P.  133°. 

For  other  variations  of  this  synthesis  the  reader 
must  be  referred  to  the  original  literature.3 

(b)  CLAISEN'S  SYNTHESIS.  Aldehydes  can  be 
made  to  condense  with  the  esters  (best  the  methyl 
esters)  of  acids  of  the  type  R.CH2COOH,  unsaturated 
acids  being  formed  with  the  loss  of  water  : 

R.CHO  +  R'.CH2COOMe  = 

R.CH=CR'.COOMe  +  H2O. 

1  B.   16,   1436.  2  B.  31,  2604. 

3  B.  15,  2048;  26,  2080;  27,  1225,  1574;  A.  216,  26; 

2l8,  121,  145  ;  227,  48  ;  256,  50  ;  283,  82  ;  361,  96  ; 

A.  Ch.  [6],  29,  433  ;  M.  17,  218  ;  18,  722  ;  D.R.P.  156,560, 
164,296,  161,171,  &c. 


1 68      PREPARATION  OF  ORGANIC  COMPOUNDS 

As  in  Perkin's  synthesis,  it  is  always  the  a-hydrogen 
atoms  of  the  ester  that  react.  The  condensation  is 
brought  about  (i)  by  metallic  sodium,  ammonia,  or 
organic  bases,  such  as  diethylamine,  piperidine, 
quinoline,  &c.,  in  which  case  only  aromatic  aldehydes 
can  be  used  ;  or  (ii)  by  hydrochloric  acid  or  acetic 
anhydride,  in  which  case  aliphatic  or  aromatic  aldehydes 
can  be  used,  and  in  the  case  of  malonic  and  aceto- 
acetic  esters,  ketones.  Just  as  in  Perkin's  synthesis, 
malonic  and  acetoacetic  esters  show  great  reactivity. 

PREPARATION  OF  ETHYL  CINNAMATE  (C6H5CH  : 
CH.COOEt).  Twenty-three  grammes  of  sodium  in  the  form 
of  thin  slices,  wire,  or  powder  (see  p.  33)  are  added  to  50  grm. 
of  pure,  dry  ethyl  acetate,  the  whole  being  well  cooled  with 
ice.  Ten  grammes  of  benzaldehyde  are  then  slowly  added, 
the  whole  shaken  occasionally  until  all  the  sodium  has  dis- 
solved, and  then  allowed  to  stand  for  two  hours.  Dilute 
acetic  acid  is  then  added,  and  the  ester  layer  collected  by  means 
of  a  separating  funnel.  It  is  washed  with  dilute  sodium  car- 
bonate solution,  dried  with  calcium  chloride,  and  then  frac- 
tionated. Ethyl  cinnamate  forms  a  colourless  liquid  boiling 
at  271°. 

PREPARATION    OF   BENZALMALONIC    ESTER 
/COOEt 

C  :  CHPh.         (a)  l  Sixteen  grammes  of  diethyl  malonate  and 

\COOEt 

10-5  grm.  of  benzaldehyde  are  mixed,  and  then  saturated 
with  dry  hydrochloric  acid  gas,  the  temperature  not  being 
allowed  to  rise  above  o°.  After  standing  for  eight  days  the 
mixture  is  well  washed  with  water,  dried,  and  fractionated 
in  vacua.  The  ester  passes  over  at  i85°-i9O°  at  12  mm. 
pressure. 

(b)  The  above  mixture  is  heated  with  10  grm.  of  acetic 
anhydride  to  150°-!  60°  for  eight  to  ten  hours   in  a    closed 
vessel.     The  product  is  worked  up  as  before. 

(c)  2  Sixteen  grammes  of  malonic  ester  and  10  grm.  of  benz- 
aldehyde are  mixed  and  then  treated  with  about  2  grm.  of 
ammonia  in  alcoholic  solution.     When  the  benzaldehyde  has 

i  A.  218,   156.  2  D.R.P.  97,734- 


THE  CARBOXYLIC  ACIDS  169 

all  disappeared,  the  product  is  washed,  first  with  water,  then 
with  dilute  hydrochloric  acid,  and  finally  again  with  water. 
It  is  then  dried,  and  fractionated  in  vacua. 

Just  as  in  Perkin's  synthesis,  ortho-hydroxyl  groups 
lead  to  lactones. 

PREPARATION  OF  COUMARIN   CARBOXYLIC  ESTER,i 

O CO 

C6H4<^  Eighty    grammes  of  malonic  ester 

XCH=C— COOEt. 

and  6 1  grm.  of  salicylic  aldehyde  are  mixed  with  15  grm. 
of  8  per  cent,  alcoholic  ammonia  solution,  or  with  I  grm.  of 
piperidine.  The  ester  slowly  separates  out  in  the  crystalline 
condition,  and  after  standing  several  days  is  collected  and 
recrystallised.  It  melts  at  94°.  Yields  80  and  90  per  cent., 
according  to  the  condensing  agent  (ammonia  or  piperidine) 
used. 

Condensation  between  two  molecules  of  an  ester,  or 
between  a  molecule  of  an  ester  and  a  molecule  of  a 
ketone,  has  been  discussed  under  ketones  (see  p.  131). 


8.  FROM  ACETOACETIC  OR  MALONIC  ESTERS 
AND  ALKYL  HALIDES 

Acetoacetic  ester,  like  other  /3-diketonic  compounds, 
forms  a  mono-sodium  salt  on  treatment  with  metallic 
sodium  : 

CH3CO.CH2.COOEt  +  Na  = 

CH3CO.CHNa.COOEt  +  H. 

This  on  treatment  with  alkyl  halides  splits  out 
sodium  halide  and  gives  an  alkyl  acetoacetic  ester  : 

CH3CO.CHNaCOOEt  +  RHlg  = 

CH3CO.CHR.COOEt  +  NaHlg. 

The  second  hydrogen  atom  can  then  be  replaced 
by  sodium,  and  this  in  turn  by  another  alkyl  group, 

i  B.  31,  2593. 


1 70      PREPARATION  OF  ORGANIC  COMPOUNDS 

which  may  or  may  not  be  the  same  as  the  first  one 
introduced.  These  reactions  lead  to  ketonic  esters. 
The  chief  importance  of  these  compounds,  however, 
lies  in  their  behaviour  when  hydrolysed.  When  the 
hydrolysis  is  carried  out  with  dilute  aqueous  alkali, 
the  carboxylic  group  is  eliminated  and  a  ketone 
formed  (ketonic  hydrolysis,  see  p.  134),  but  when  the 
hydrolysis  is  brought  about  by  concentrated  aqueous 
or  alcoholic  potash,  acetic  acid  and  a  substituted 
acetic  acid  arc  formed  ("  acid  hydrolysis  ") : 

CH3.CO.CRR'.COOEt  +  2KOH  = 

CHSCOOK  +  CHRR'.COOK  +  EtOH. 

It  is  impossible,  however,  to  carry  out  the  acid 
hydrolysis  to  the  complete  exclusion  of  ketonic 
decomposition. 

PREPARATION     OF     HEXANE-3-CARBOXYLIC      ACID, 

>CH  .  COOH.1       One   atomic    proportion    of 


C2H5 

\< 


CHg.CH2.CH2/ 

sodium  is  dissolved  in  10  to  12  parts  of  absolute  alcohol, 
and  after  the  solution  has  cooled,  one  molecular  proportion 
of  acetoacetic  ester  added.  Rather  more  than  one  molecule  of 
ethyl  iodide  is  then  run  in  slowly  through  a  reflux  condenser. 
When  all  the  iodide  has  been  added,  the  whole  is  heated  on 
the  water-bath  until  it  no  longer  reacts  alkaline  to  moist 
litmus  paper.  If  this  result  cannot  be  reached  more  ethyl 
iodide  must  be  added.  The  solution  now  contains  ethyl 
acetoacetic  ester  (see  p.  134).  Another  atomic  proportion  of 
sodium  dissolved  in  alcohol  is  then  added,  and  then  rather 
more  than  a  molecular  proportion  of  n.-propyl  iodide  is  dropped 
in,  and  the  whole  heated  as  before  until  neutral.  The  solution 
now  contains  ethyl-  w.-propyl  acetoacetic  ester  : 


CH3  .  CO—  CCOOEt 

\CH2.CH2.CH3. 

The  greater  part  of  the  alcohol  is  removed  by  distillation 
from  the  water-bath,  and  the  residue  shaken  with  water  until 
all  the  solid  matter  has  dissolved.  The  ester  is  then  extracted 

i  B.  19,  227. 


THE  CARBOXYLIC  ACIDS  171 

with  ether,  the  ethereal  solution  dehydrated  with  anhydrous 
sodium  sulphate,  and  the  ether  removed  by  distillation.  The 
residue  is  heated  until  the  temperature  reaches  145°. 

To  bring  about  its  hydrolysis,  i  part  of  the  ester  is  heated 
with  a  free  flame  under  a  reflux  condenser  for  four  hours  with 
2  parts  of  caustic  potash  dissolved  in  J  part  of  water  and  J  part 
of  alcohol.  The  whole  is  then  diluted  with  water,  ethyl 
propyl  ketone,  a  by-product  due  to  the  ketonic  hydrolysis 
taking  place  as  a  side-reaction,  and  unchanged  ester  extracted 
with  ether,  and  the  liquid  then  acidified.  The  hexane-3- 
carboxylic  acid  separates  out  as  an  oil  and  is  collected,  dried, 
and  distilled.  B.P.  209°. 

A  synthesis  similar  to  the  above  can  be  carried  out 
with  malonic  ester,  and  this  synthesis  has  the  advantage 
that  the  hydrolysis  can  only  go  in  one  direction  : 

.COOEt 

RR'.C<  +3KOH  = 

\COOEt 

RR'.CHCOOK  +  K2C03  +  2EtOH. 

Just  as  in  the  case  of  ac$ toacetic  ester,  only  one  atom 
of  sodium  can  be  introduced  into  malonic  ester  at  a 
time.1  In  this  case  also  only  alky  I  and  not  aryl  halides 
can  be  used. 

The  hydrolysis  is  brought  about  by  concentrated 
caustic  potash,  hydrochloric  acid,  or  50  'per  cent. 

1  It  was  pointed  out  on  p.  136  that  dialkyl  compounds  are 
frequently  formed  when  acetoacetic  ester  is  treated  with  one 
molecule  of  sodium  and  one  molecule  of  alkyl  halide.  This 
also  happens  in  the  case  of  malonic  ester  : 

RCH(COOEt)2  +  CHNa  ^±  RCNa(COOEt)2  +  CH2(COOEt)2 
RCNa(COOEt)2  +  RI  =  R2C(COOEt)2  +  Nal. 

By  using  only  half  the  calculated  quantity  of  sodium  and 
alkyl  halide,  the  yield  of  the  monoalkyl  compound  is  usually 
improved.  Thus  when  malonic  ester  is  treated  with  one 
molecule  of  sodium  and.  one  molecule  of  benzyl  chloride,  the 
yield  of  the  benzyl  derivative  is  only  55  per  cent.,  whereas 
when  only  half  a  molecule  of  sodium  and  half  a  molecule  of 
benzyl  chloride  are  used  the  yield  is  85  per  cent.  B.  44,  1507. 


172      PREPARATION  OF  ORGANIC  COMPOUNDS 

sulphuric  acid,  or  the  free  malonic  acid  derivative  is 
heated  alone. 

PREPARATION    OF    ETHYL    MALONIC     ESTER    (C2H5 

CE^COOEty.1  One-tenth  of  a  gramme- molecule  (2-3  grm.)  of 
sodium  is  dissolved  in  25  grm.  of  absolute  alcohol,  and  16  grm. 
of  malonic  ester  added  to  the  cooled  solution.  Twenty 
grammes  of  ethyl  iodide  are  then  slowly  added  through  a  reflux 
condenser,  and  the  whole  heated  on  the  water-bath  until  it 
no  longer  reacts  alkaline  to  moist  litmus  (one  to  two  hours). 
The  alcohol  is  then  distilled  off,  and  the  residue  shaken  with 
water  until  all  the^solid  matter  has  dissolved.  The  ester  is 
then  extracted  with  ether,  the  ethereal  solution  dried  with 
anhydrous  sodium  sulphate,  the  ether  distilled  off,  and  the 
residual  oil  fractionated.  B.P.  2o6°-2o8°.  Yield  15  grm. 

PREPARATION  OF  BUTYRIC  ACID  (C2H5CH2COOH).2 
Ten  grammes  of  the  above  ester  (ethyl  diethyl  malonate)  are 
slowly  added  to  a  cold  solution  of  12-5  grm.  of  caustic  potash 
in  10  c.c.  of  water.  The  emulsion  thus  obtained,  when  gently 
warmed  under  a  reflux,  suddenly  boils  up.  The  boiling  is 
continued  until  the  oily  layer  has  disappeared.  The  solution 
is  then  diluted  with  twice  its  volume  of  water,  acidified  with 
concentrated  hydrochloric  acid  (use  Congo  paper),  and  extracted 
with  ether,  the  ethereal  solution  dried  and  distilled.  The 
ethyl  malonic  acid,  C2H6CH(COOH)2,  is  left  behind  as  a  crystal- 
line mass,  which  melts  at  112°.  Yield  5  grm.  On  heating 
to  1 80°  for  an  hour  it  loses  carbon  dioxide  to  form  butyric 
acid,  which  can  then  be  distilled  off.  Butyric  acid  boils  at 
i62°-i63°,  and  has  a  disgusting,  rancid  odour. 

By  boiling  ethyl  diethyl  malonate  for  several  hours  with 
50  per  cent,  sulphuric  acid,  the  hydrolysis  of  the  ester  and  the 
loss  of  carbon  dioxide  take  place  simultaneously. 

ADDENDA 

The  Benzilic  Acids.  When  an  aromatic  aldehyde  is 
heated  with  potassium  cyanide  in  alcoholic  solution, 
condensation  takes  place  and  a  hydroxy-ketone  is 
formed  (see  p.  131) : 

zAr.CHO  =  ArCHOH.CO.Ar. 
1  A.  204,  127,134.  2  Loc.  cit. 


THE  CARBOXYLIC  ACIDS  173 

This  on  oxidation  (nitric  acid)  gives  the  corresponding 
a-diketone  (see  p.  123) : 

Ar.CHOH.CO.Ar  +  O  =  ArCO.CO.Ar  +  H2O 

which  on  fusion  with  caustic  alkali  takes  up  the  ele- 
ments of  water  and  undergoes  a  complete  rearrangement, 
a  diaryl  glycollic  acid  (benzilic  acid)  being  formed  : 

Ar .  CO .  CO .  Ar  +  H20  =  Ar2COH .  COOH. 

PREPARATION  OF  BENZILIC  ACID  (C6H6)2.COH. 
COOH.1  Fifty  grammes  of  caustic  potash  are  dissolved  in 
100  c.c.  of  water,  and  125  c.c.  of  alcohol  then  added.  Fifty 
grammes  of  benzil  are  added  to  the  solution  thus  obtained, 
and  the  whole  heated  on  the  water-bath  under  a  reflux  con- 
denser. The  heating  is  continued  for  ten  to  twelve  minutes 
after  ebullition  has  set  in,  but  longer  heating  must  be  carefully 
avoided.  The  contents  of  the  flask  are  poured  into  a  beaker, 
allowed  to  stand  for  several  hours,  and  then  filtered.  The 
precipitate  is  washed  with  a  little  alcohol  and  then  removed  from 
the  paper  and  violently  shaken  with  100  c.c.  of  cold  alcohol. 
It  is  filtered,  drained  at  the  pump  as  completely  as  possible, 
and  then  dissolved  in  cold  water  (500-1000  c.c.)  and  filtered. 
The  filtrate  is  heated  to  boiling  and  acidified  with  boiling 
dilute  sulphuric  acid  (use  Congo  paper).  The  benzilic  acid 
separates  out  on  cooling  and  is  washed  with  cold  water.  It 
forms  colourless  needles  melting  at  150°.  Yield  90  to  95  per 
cent.  This  method  gives  better  results  than  the  older  method 
of  fusing  with  caustic  potash  (5  parts)  at  150°. 

The  o.-benzoyl  benzoic  acids  are  obtained  from 
phthalic  anhydride  and  an  aromatic  hydrocarbon  or 
a  substitution  product,  in  the  presence  of  aluminium 
chloride.  The  yields  are  excellent  (go  to  95  per  cent. 
as  a  rule).  The  reaction  has  been  discussed  on  p.  129. 

The  sym.-diphenyl  methane  dicarboxylic  acids  are 
obtained  by  condensing  benzoic  acid,  &c.,  with  formalde- 
hyde in  the  presence  of  mineral  acids  (Lederer-Manasse 
synthesis.  Cf.  p.  97).  The  condensation  takes  place 
in  the  meta-  position. 

PREPARATION  OF  DIPHENYL  METHANE-s.s'-DICARB- 
OXYLIC  ACID.2  Twenty-five  grammes  of  benzoic  acid  are 

i  B.  41, 1644.  2  B.  27, 2324,  3315. 


174      PREPARATION  OF  ORGANIC  COMPOUNDS 

mixed  with  125  grm.  of  concentrated  sulphuric  acid,  and  the 
whole  well  cooled.  Ten  cubic  centimetres  of  40  per  cent. 
formaldehyde  solution  are  then  added  slowly,  and  the  whole 
allowed  to  stand  for  four  days  at  a  temperature  of  30°.  It  is 
then  poured  into  water,  and  the  precipitate  collected,  washed 
with  cold  water  and  recrystallised  from  chloroform.  It  forms 
colourless  tablets  which  melt  with  decomposition  at  118°- 
119°. 

THE  ACID  ANHYDRIDES 

For  convenience  the  acid  anhydrides  can  be  divided 
into  two  classes,  viz.  (i)  anhydrides  formed  by  the  loss 
of  water  between  two  carboxyl  oups  in  the  same 
molecule  ;  (2)  anhydrides  formed  by  the  loss  of  water 
between  two  carboxyl  groups  in  different  molecules. 

The  first  class  of  anhydrides  is  formed  only  by  poly- 
basic  aliphatic  acids  whose  carboxyl  groups  are  sepa- 
rated by  two  or  three  carbon  atoms,  i.e.  acids  of  the 
succinic,  maleic,  and  glutaric  groups,  and  by  aromatic 
or^o-dicarboxylic  acids,  e.g.  phthalic  acid.  This  latter 
rule  is  not  absolute,  as  terephthalic  acid  (1-4)  forms 
an  anhydride,  but  only  with  great  difficulty.  These 
anhydrides  are,  as  a  rule,  very  readily  formed  simply 
by  heating  the  acid  alone  or  with  a  dehydrating  agent, 
such  as  sulphuric  acid.  The  greater  number  of 
anhydrides  belong  to  the  second  class  and  may  be 
regarded  as  diacyl  derivatives  of  water.  They  are 
formed  : 

i.  BY  HEATING  THE  ACID  WITH  ACETIC 
ANHYDRIDE 

PREPARATION  OF  CINNAMIC  ANHYDRIDE  (C6H5CH  = 
CH.CO)2O.1  Fifty  grammes  of  cinnamic  acid  and  200  grm. 
of  acetic  anhydride  are  boiled  under  a  reflux  condenser  for 
six  hours.  The  liquid  is  then  distilled  until  the  temperature 
reaches  146°,  and  the  residue,  after  cooling,  taken  up  with 
ether.  On  evaporating  off  the  ether,  the  anhydride  separates 
in  the  crystalline  state.  It  may  be  recrystallised  from  alcohol, 
and  forms  colourless  needles  which  melt  at  136°, 

i  B.  34,  186,  2074. 


THE  CARBOXYLIC  ACIDS  175 

2.  BY  HEATING  THE  ACID  CHLORIDE  WITH 
THE  ANHYDROUS  SODIUM  SALT 


CH3.CO.O  jNa     CljCO.CH3          — >          (CH3CO)2O. 

This  reaction  usually  takes  place  with  great  ease. 
On  the  manufacturing  scale  the  chloride  is  not  isolated, 
but  the  sodium  salt  is  treated  with  half  the  quantity  of 
phosphorus  oxychloride,  &c.,  requisite  for  its  complete 
conversion  into  the  acid  chloride.  In  the  laboratory, 
however,  it  is  always  best  to  isolate  the  chloride. 

PREPARATION  OF  ACETIC  ANHYDRIDE  (CH3CO)2O. 
Fifty  grammes  of  well-powdered  anhydrous  sodium  acetate 
are  placed  in  a  retort,  and  35  grm.  of  acetyl  chloride  slowly 
dropped  in,  the  retort  being  well  cooled  with  water  and  shaken 
from  time  to  time.  When  all  the  chloride  has  been  added,  the 
whole  is  distilled  until  no  more  liquid  passes  over,  the  distillate 
being  collected  in  a  receiver  provided  with  a  calcium  chloride 
tube  to  exclude  atmospheric  moisture.  The  distillate  is  then 
redistilled  over  a  little  fresh  anhydrous  sodium  acetate.  The 
anhydride  forms  a  pungent -smelling  liquid  boiling  at  136°- 
137°.  Yield  about  40  grm. 

3.  BY  TREATING  THE  ACID  CHLORIDE  WITH 
QUINOLINE  OR  PYRIDINE1 

In  this  reaction  an  addition  product  is  first  formed, 
which  then  reacts  with  water,  hydrochloric  acid 
and  the  acid  anhydride  being  formed.  In  other 
words,  diacyl  derivatives  of  water  can  be  obtained 
by  the  action  of  acid  chlorides  on  water  under  the 
influence  of  pyridine  or  quinoline. 

PREPARATION  OF  BENZOIC  ANHYDRIDE  (C6H5CO)2O.2 
Twenty-five  grammes  of  benzoyl  chloride  are  slowly  added  to 
10  c.c.  of  pyridine  and  8  grm.  of  anhydrous  sodium  carbonate. 
After  standing  for  half  an  hour  the  whole  is  poured  into 
water,  and  the  precipitated  benzoic  anhydride  filtered  off  and 

1  B.  34,  2070  ;    D.R.P.  117,267. 

2  G.22  [2],  215;   J.pr.  [2],  50,  479. 


176      PREPARATION  OF  ORGANIC  COMPOUNDS 

washed  with  cold  water.  By  dissolving  the  dried  product 
(use  a  vacuum  desiccator)  in  petroleum  ether,  and  then  evapo- 
rating the  solution  at  the  ordinary  temperature  in  vacua, 
the  anhydride  is  obtained  as  long  colourless  needles  which 
melt  at  42°. 

THE  CARBOXYLIC  ESTERS 

In  this  section  only  methods  for  converting  the  carb- 
oxylic  acid  (or  the  acid  chloride  or  anhydride)  into 
the  corresponding  ester  will  be  considered.  The  forma- 
tion of  esters  by  building  up  from,  or  degrading  other 
esters  will  be  found  discussed  elsewhere. 

Just  as  the  alcohols  may  be  regarded  as  analogous 
to  the  inorganic  alkaline  hydroxides,  so  may  the 
esters  be  regarded  as  analogous  to  the  inorganic 
salts  : 

*O 
R.COOH  +  HOR'  =  R.C^-0— R'  +  H2O. 

Polybasic  acids  form  neutral  and  acid  esters,  analo- 
gous to  the  neutral  and  acid  inorganic  salts.  Poly- 
hydric  alcohols  usually  form  both  mono-  and  poly-acyl 
derivatives,  corresponding  to  the  basic  and  neutral 
salts.  The  alcohols  also  form  esters  with  inorganic 
acids,  some  of  which  will  be  found  discussed  at  the  end 
of  this  chapter. 

The  alcohols  must  be  regarded  as  very  weak  bases, 
and  hence,  as  would  be  expected,  their  salts,  the  esters, 
are  readily  hydrolysed  by  water,  just  as  inorganic 
salts  formed  from  weak  bases,  such  as  Fe(OH)3,  A1(OH)3, 
are  slowly  decomposed  into  their  components  by 
water.  In  other  words,  the  reaction  indicated  by  the 
equation  given  above  is  reversible,  and  can  only  be 
completed  by  continually  removing  one  of  the  products,, 
formed.  When  the  alcohol,  acid,  and  ester  all  boil 
at  a  high  temperature,  this  can  be  done  by  heating 
the  reaction  mixture  in  an  open  vessel  so  that  the 
water  is  removed  as  vapour.  As  a  rule,  however, 
some  dehydrating  agent  is  added  to  the  reaction 
mixture. 


THE  CARBOXYLIC  ACIDS  177 

i.   ESTERIFICATION   OF   THE   FREE   ACID   BY 
THE  ALCOHOL 

The  alcohol  and  the  acid  are.  mixed  together,  and 
the  solution  saturated  with  dry  hydrochloric  acid  gas 
and  then  allowed  to  stand,  or  sulphuric  acid  is  added 
and  the  ester  distilled  off  as  it  is  formed. 

PREPARATION  OF  ETHYL  ACETATE  (CH3COOC2H5). 
Fifty  cubic  centimetres  of  absolute  alcohol  are  slowly  mixed 
with  an  equal  volume  of  concentrated  sulphuric  acid,  and  the 
whole  distilled  from  an  oil-bath  at  140°.  During  the  distilla- 
tion a  mixture  of  100  c.c.  of  glacial  acetic  acid  and  100  c.c.  of 
alcohol  is  dropped  into  the  flask  from  a  tap-funnel  at  the 
same  rate  as  liquid  collects  in  the  receiver.  When  the  whole 
of  the  latter  mixture  has  been  added,  the  distillate  is  shaken 
up  with  strong  sodium  carbonate  solution  until  the  upper  layer 
is  no  longer  acid  (use  moist  litmus  paper).  The  layers  are  then 
separated.  The  upper  layer  consists  of  ethyl  acetate  mixed 
with  some  alcohol  and  ether.  The  former  of  these  is  removed 
by  shaking  with  concentrated  (40  per  cent.}  calcium  chloride 
solution.  The  ethyl  acetate  is  then  dried  with  calcium 
chloride  and  distilled  from  the  water-bath.  The  portion 
which  distils  below  75°  contains  ether  and  is  rejected.  The 
portion  boiling  between  75°  and  80°  is  ethyl  acetate,  and  is 
fairly  pure.  .Colourless,  pleasant -smelling  liquid  boiling  at 
77°.  Yield  about  80  per  cent. 

PREPARATION  OF  DIETHYL  TARTRATE  (CHOH)2 
(COOEt)2.1  Finely  powdered  tartaric  acid  is  shaken  with 
rather  more  than  its  own  weight  of  absolute  alcohol,  and  then 
saturated  with  dry  hydrochloric  acid  gas,  the  whole  being  well 
cooled  with  ice.  The  mixture  is  allowed  to  stand  for  at  least 
twenty-four  hours,  and  then  the  supernatant  liquid  poured 
off  from  the  unchanged  acid.  The  greater  part  of  the  hydro- 
chloric acid  is  removed  from  the  solution  by  blowing  air 
through  it.  The  excess  of  alcohol  and  water  is  then  removed 
by  distilling  in  vacua  from  the  water-bath.  The  residue 
consists  chiefly  of  the  acid  ester.  It  is  taken  up  with  the  same 
amount  of  absolute  alcohol  as  was  used  previously,  and  the 
well-cooled  solution  again  saturated  with  hydrochloric  acid. 

i  B.  13,  1176. 

12 


1 78  PREPARATION  OF  ORGANIC  COMPOUNDS 

After  standing,  it  is  treated  exactly  as  before,  and  the  residue, 
which  does  not  distil  from  the  water-bath,  then  fractionated 
in  vacua.  After  refractionation  the  ester  forms  a  colourless 
viscous  liquid  which  boils  at  155°  at  n  mm.  and  162°  at 
19  mm.  It  solidifies  on  prolonged  standing  to  a  mass  of 
colourless  crystals  which  melt  at  48°. 

PREPARATION  OF  ETHYL  BENZOATE  (C6H5COOEt). 
Twenty-five  grammes  of  benzoic  acid  are  boiled  under  a  reflux 
condenser  with  100  c.c.  of  5  per  cent,  absolute  alcoholic  hydro- 
chloric acid  solution  until  on  pouring  a  sample  into  water, 
only  an  oil  and  no  solid  matter  separates  out  (about  two  hours). 
The  excess  of  alcohol  is  then  distilled  off  from  the  water-bath, 
and  the  residue  poured  into  water  and  made  slightly  alkaline 
with  sodium  carbonate.  The  ester,  which  separates  as  an 
oil,  is  collected,  dried  with  calcium  chloride,  and  distilled.  It 
forms  a  colourless  liquid  which  boils  at  211°.  Yield  about 
80  per  cent. 


2.  BY  THE  ACTION  OF  THE  ACID  CHLORIDE 
ON  THE  ALCOHOL 

This  method  is  especially  useful  in  preparing  the 
aromatic  esters.  In  this  case  the  phenol  is  dissolved 
in  excess  of  cold,  10  per  cent,  caustic  soda  and  the 
solution  shaken  with  excess  of  the  acid  chloride  until 
the  latter  has  disappeared  (Schotten-Baumann 
method).  The  ester  is  then  collected  and  purified. 
Instead  of  caustic  soda,  sodium  carbonate,  chalk, 
barium  carbonate,  &c.,  may  be  used,  and  this  modi- 
fication is  often  useful  when  working  with  phenols 
which  are  sensitive  to  alkali.  Pyridine  also  can  be 
used  and  generally  gives  excellent  results,  but  in  some 
cases  the  product  is  not  identical  with  that  obtained 
when  an  inorganic  base  is  employed.  Thus  erythrite 
when  treated  with  benzoyl  chloride  in  the  presence  of 
caustic  alkali  gives  only  a  tribenzoate,  but  in  the 
presence  of  pyridine  di-,  tri-,  and  tetra-benzoates  are 
all  formed. 

Esterification  in  the  presence  of  p}7ridine  is  usually 
carried  out  by  dissolving  the  alcohol  or  phenol  in 


THE  CARBOXYLIC  ACIDS  179 

5  to  10  parts  of  pyridine,  and  then  adding  the  acid 
chloride,  the  whole  being  well  cooled.  After  eight 
hours  the  reaction  mixture  is  poured  slowly  into  cold 
dilute  sulphuric  acid,  and  the  ester  collected  and 
purified. 

A  full  discussion  of  the  above  methods  will  be  found 
in  Lassar-Cohn's  "  Arbeitsmethoden." 

PREPARATION  OF  PHENYL  BENZOATE  (C6H6O. 
COC6H5).  Five  grammes  of  phenol  are  dissolved  in  70  c.c. 
of  10  per  cent,  caustic  soda  at  25°-3o°.  Five  grammes  of 
benzoyl  chloride  are  then  added,  and  the  whole  violently 
shaken  until  the  smell  of  benzoyl  chloride  has  vanished. 
The  ester  is  then  filtered  off,  washed  with  cold  water,  and  re- 
crystallised  from  alcohol.  It  forms  colourless  crystals  melting 
at  68°-69°. 

Instead  of  phenol,  the  cresols,  naphthols,  &c.,  may 
be  used.  With  alcohols  the  reaction  takes  place  even 
more  readily. 

It  is  not  necessary  to  isolate  the  acid  chloride  in  a 
pure  state,  but  the  crude  substance  prepared  from  the 
acid  or  its  sodium  salt  can  be  used  directly. 

PREPARATION     OF     DIMETHYL      TEREPHTHALATE, 

C6H4    TAT  -1     Crude   terephthalic   acid  is   warmed   with 


two  molecules  of  phosphorus  pentachloride  until  the  mass 
becomes  liquid  .  Excess  of  methyl  alcohol  is  then  added,  and 
the  whole  boiled  under  a  reflux  condenser  for  an  hour.  On 
cooling,  the  ester  crystallises  out.  It  melts  at  140°.  Yield 
90  per  cent. 

PREPARATION    OF    MANNITOL    DIBENZOATE.*     Two 

grammes  of  mannitol  are  dissolved  in  120  c.c.  of  pyridine,  and 
9-3  grm.  of  benzoyl  chloride  slowly  dropped  into  the  slightly 
warm  solution.  After  standing  some  hours,  the  whole  is 
poured  into  cold  dilute  sulphuric  acid,  the  ester  collected, 
washed  with  cold  water,  and  then  recrystallised  from  alcohol. 
Colourless  needles  melting  at  178°. 

i  A.  245,  140.     Cf.  also  J.  pr.  [2],  20,  263  ;    D.R.P.  38,973, 
70,483,  71,446.  2  A.  301,  102. 


i8o      PREPARATION  OF  ORGANIC  COMPOUNDS 

The  above  methods  can  also  be  employed  for  pre- 
paring the  esters  of  sulphonic  acids  from  their 
chlorides. 

3.   BY  THE  ACTION   OF  THE  ACID   ANHYDRIDE 
ON  THE  ALCOHOL 

In  practice  this  method  is  almost  confined  to  the 
preparation  of  acetates.  The  esterification  is  brought 
about  by  boiling  the  alcohol  or  phenol  with  acetic 
anhydride,  alone  or  in  glacial  acetic  acid  solution,  with 
or  without  the  addition  of  a  dehydrating  agent  such  as 
sulphuric  acid,  anhydrous  sodium  acetate,  or  anhydrous 
zinc  chloride.  Other  variations  of  the  method  are 
known,  for  which  the  reader  is  referred  to  larger 
works.1 

PREPARATION  OF  MANNITOL  HEXA-ACETATE 

(CH2OCOCH3)2.(CHOCOCH3)4.2  Ten  grammes  of  mannitol 
are  added  to  40  grm.  of  acetic  anhydride,  and  then  a  little  anhy- 
drous zinc  chloride  added.  Considerable  heat  is  evolved,  and 
when  the  reaction  has  moderated,  the  whole  is  heated  on  the 
water -bath  for  a  short  time,  and  after  cooling  poured  into  cold 
water.  The  ester  is  collected,  washed  with  cold  water,  and 
then  recrystallised  from  ether  or  from  a  mixture  of  alcohol 
and  ethyl  acetate.  It  forms  colourless  rhombic  crystals 
which  melt  at  119°, 

4.  ESTERIFICATION  WITH  METHYL  SULPHATE 

This  method  is,  of  course,  limited  to  the  production 
of  methyl  esters.3  It  usually  gives  excellent  results, 
but  great  care  must  be  exercised  as  methyl  sulphate 
is  very  poisonous.4  The  process  is  carried  out 
either  by  shaking  the  free  acid  with  methyl  sulphate 
and  excess  of  cold  dilute  caustic  soda  for  half  an  hour, 

*  See  Lassar  Cohn,  "  Arbeitsmethoden, "  4th  ed.  1907, 
p.  15  et  seq.,  and  p.  238  et  seq. 

2  B.  12,  2059. 

3  It  should  be  noted  that  diethyl  sulphate  is  utterly  useless 
for  preparing  ethyl  esters,  &c. 

4  See  p.  183, 


THE  CARBOXYLIC  ACIDS  181 

and  then  warming  the  mixture  on  the  water-bath  for 
half  an  hour,  or  the  dry  potassium  salt  of  the  acid  is 
heated  with  methyl  sulphate  (if  molecules)  until  no 
more  ester  distils  over.  This  method,  however,  is  only 
used  when  other  methods  fail.  It,  however,  affords  a 
convenient  method  of  preparing  methyl  iodide.  (Slowly 
drop  126  grm.  of  dimethyl  sulphate  into  a  solution  of 
166  grm.  of  potassium  iodide  in  166  c.c.  of  water  heated 
on  the  water-bath.  The  methyl  iodide  distils  over 
in  90  per  cent,  yield.  D.R.P.  175,209.) 

5.  FROM  THE  SILVER  SALT  OF  THE  ACID  AND 
THE  ALKYL  IODIDE 

This  method  is  only  employed  when,  owing  to 
steric  or  other  causes,  the  acid  cannot  be  esterified  by 
the  usual  methods.  The  iodide  or  other  halide  is 
dissolved  in  some  suitable  solvent  (benzene,  xylol,  &c.), 
and  shaken  or  heated  with  the  silver  salt.  The  silver 
halide  is  then  filtered  off  and  the  filtrate  fractionated. 

THE  ESTERS  OF  INORGANIC  ACIDS 

The  esters  of  the  halogen  acids  (the  alkyl  and  aryl 
halides)  have  been  fully  discussed  in  Chapter  III. 

Of  the  esters  of  nitric  acid,  glycerine  trinitrate 
(nitroglycerine),  and  various  cellulose  nitrates  (nitro- 
cottons,  gun-cotton,  collodion,  pyroxylin,  &c.),  are 
prepared  by  the  action  of  concentrated  nitric  and 
sulphuric  acids  on  glycerine  and  cellulose  (cotton 
waste)  respectively.  They  are  used  in  enormous 
quantities  in  the  manufacture  of  explosives,  celluloid, 
photographic  films,  artificial  silk,  &c.,  but  cannot  be 
safely  prepared  in  the  laboratory.  Some  of  the  esters 
of  nitrous  acid,  especially  amyl  nitrite  (amylium 
nitrosum)  and  ethyl  nitrite  (spiritus  setheris  nitrosi), 
are  of  therapeutic  value  owing  to  their  dilating  the 
blood-vessels  and  thus  lowering  the  blood-pressure. 
Amyl  nitrite  is  also  useful  for  preparing  diazo-com- 
pounds. 


1 82      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  AMYL  NITRITE  (C,HuONO).i 
Thirty  grammes  of  fermentation  amyl  alcohol  are  cautiously 
mixed  with  an  equal  weight  of  concentrated  sulphuric  acid, 
the  mixture  well  cooled,  and  then  slowly  added  to  a  cooled 
mixture  of  26  grm.  of  potassium  nitrite  and  15  c.c.  of  water. 
The  whole  is  then  cautiously  distilled .  The  amyl  nitrite  passes 
over  below  100°,  and  is  well  washed  with  water.  It  is  finally 
dried  over  calcium  chloride  and  again  distilled.  Yellowish 
liquid,  B.P.  96°.  Great  care  should  be  taken  not  to  inhale  its 
vapour  as  it  has  a  powerful  action  on  the  heart . 

Some  of  the  esters  of  sulphuric  acid  are  of  importance, 
especially  dimethyl  sulphate.  By  the  action  of  con- 
centrated sulphuric  acid  on  alcohols,  alkyl  sulphuric 
acids  are  formed  : 

R.OH  +  H2S04  =  R.SO3.OH  +  H2O. 

Excess  of  sulphuric  acid  is  then  removed  with 
lead,  calcium,  or  barium  carbonate,  and  the  soluble 
metal  alkyl  sulphate  either  obtained  by  evaporating 
the  filtrate  or,  if  the  free  acid  is  required,  exactly  the 
required  amount  of  sulphuric  acid  is  added,  and  the 
filtrate  then  concentrated. 

PREPARATION  OF  POTASSIUM  ETHYL  SULPHATE 
(C2H5O.SO2.OK).  Fifty  grammes  of  absolute  alcohol  are 
slowly  run  into  36  grm.  of  concentrated  sulphuric  acid,  the 
whole  being  well  stirred  during  the  operation.  Considerable 
heat  is  evolved,  and  the  rate  at  which  the  alcohol  is  added  is 
regulated  so  that  the  temperature  rises  to  8o°-9o°.  When  all 
the  alcohol  has  been  added,  the  whole  is  heated  on  the  water- 
bath  for  three  hours  under  a  reflux  condenser.  After  cooling, 
the  reaction  mixture  is  poured  into  about  500  c.c.  of  cold  water 
and  neutralised  (use  litmus)  with  a  slight  excess  of  chalk  or  lead 
carbonate  ground  to  a  thin  cream  with  water.  The  mixture 
is  filtered  boiling,  and  the  precipitate  washed  with  boiling 
water.  The  clear,  boiling  filtrate  is  then  treated  with  con- 
centrated potassium  carbonate  solution  until  no  more  pre- 
cipitation takes  place  (test  a  filtered  sample  from  time  to  time), 
filtered,  and  the  filtrate  concentrated  until  crystallisation 

1   J-  1874,  352. 


THE  CARBOXYLIC  ACIDS  183 

sets  in.     On  cooling,  the  potassium  salt  separates  out  and  is 
filtered  off  and  washed  with  a  little  alcohol. 

The  above  recipe  can  also  be  used  for  preparing  potassium 
methyl  sulphate  from  methyl  alcohol. 

PREPARATION  OF  DIMETHYL  SULPHATE1  (CH3)2SO4. 
In  carrying  out  this  preparation  it  must  be  remembered  that 
dimethyl  sulphate  is  very  poisonous,  and  great  care  must  be 
taken  not  to  inhale  any  of  its  vapour.  In  spite  of  its  high 
boiling-point  the  vapours  it  emits  at  the  ordinary  temperature 
have  been  known  to  cause  death  in  several  cases.  As  it  is 
readily  absorbed  through  the  skin,  care  must  be  taken  not  to 
spill  any  on  the  hands.  Should  any  be  spilt  on  the  clothes 
these  must  be  changed  at  once.2 

One  hundred  grammes  of  chlorsulphonic  acid  are  placed  in 
a  200  c.c.  distilling-flasb  provided  with  a  rubber  stopper 
carrying  a  thermometer,  the  bulb  of  which  dips  into  the  acid, 
and  a  Walter  dropping-funnel  (see  Fig.  3,  p.  2).  The  end  of 
the  stem  of  this  latter  is  drawn  out  to  a  fine  capillary,  and  then 
bent  upwards  so  that  the  opening  is  just  below  the  surface  of 
the  acid  in  the  flask.  Twenty-seven  grammes  of  anhydrous 
methyl  alcohol  are  placed  in  the  funnel,  and  before  the  latter 
is  dipped  under  the  acid,  sufficient  alcohol  to  completely  fill 
the  capillary  is  allowed  to  drop  through  the  tap.  The  acid 
must  be  cooled  to  -  10°  before  the  reaction  is  started.  The 
side-tube  of  the  flask  is  connected  with  a  wash-bottle  containing 
a  little  concentrated  sulphuric  acid,  and  this  with  a  large  wash- 
bottle  partly  filled  with  cold  water  (to  absorb  HC1  evolved), 
a  safety-tube  being  provided  to  prevent  the  water  being  sucked 
back.  The  alcohol  is  then  slowly  dropped  in  (about  an  hour 
and  a  half  is  required),  the  flask  being  frequently  shaken  and 
care  being  taken  to  keep  the  temperature  below  -  5°.  When 
all  the  alcohol  has  been  added,  the  contents  of  the  flask  are 
distilled  in  vacua  (20  mm.)  from  an  oil-bath  at  140°.  The 
dimethyl  sulphate  which  passes  over  is  washed  with  a  little 
ice-water,  and  then  dried  with  anhydrous  sodium  sulphate. 
It  is  then  pure  enough  for  all  practical  purposes.  It  forms 
a  colourless  liquid  which  boils  at  188°  at  atmospheric 
pressure. 

1  A.  327,  105. 

2  Archives    fur    Experim.    Pathologic    u.    Pharmakologie, 
47,  115.  127. 


184      PREPARATION  OF  ORGANIC  COMPOUNDS 

The  potassium  salts  of  the  monoaryl  sulphuric 
esters  are  prepared  by  the  action  of  potassium  pyro- 
sulphate  on  the  phenols.  As  the  pyrosulphate  of 
commerce  often  gives  very  unsatisfactory  results,  it  is 
advisable  to  prepare  the  salt  immediately  before  use  by 
igniting  acid  potassium  sulphate  until  it  has  lost 
exactly  the  weight  demanded  by  the  equation  : 

2KHSO4  =  K2S2Q7  +  H2O. 


CHAPTER  VIII 
THE  NITRILES  OR  CYANIDES 

THE  nitriles  or  cyanides  contain  the  group  — CN,  and 
are  of  considerable  importance  owing  to  their  ready 
hydrolysis  to  the  corresponding  carboxylic  acids  (see 
pp.153,  224). 
They  are  obtained  by  the  following  methods  : 

i.  FROM  THE  ACID  AMIDES 

This  method  is  common  to  both  the  aliphatic  and 
aromatic  series,  the  nitrile  being  formed  by  heating 
the  amide  with  a  powerful  dehydrating  agent : 

R.C/°     =RC^N+H20 
^NH,, 

The  dehydrating  agent  most  usually  chosen  is 
phosphorus  pentoxide,  the  reaction  being  carried  out 
by  distilling  the  amide  with  this  reagent.  Phosphorus 
pentachloride  and  thionyl  chloride1  also  give  good 
results. 

PREPARATION  OF  ACETONITRILE  (CH3CN).2  Fifteen 
grammes  of  phosphorus  pentoxide  are  transferred  to  a  distilling 
flask  by  pushing  the  neck  of  the  flask  through  a  hole  in  the 
cork  of  the  pentoxide  bottle,  and  then  shaking  in  the  required 
weight.  Ten  grammes  of  dry,  finely  powdered  acetamide  are 
added  and  well  mixed  by  shaking.  The  whole  is  then  cautiously 
distilled  (the  reaction  becomes  violent  if  the  heating  is  too 
rapid)  until  nothing  more  passes  over.  The  distillate  is 
treated  with  about  half  its  volume  of  water,  solid  potassium 

1  A.  274,  312.  2  A.  64,  332. 

185 


1 86      PREPARATION  OF  ORGANIC  COMPOUNDS 

carbonate  added  until  no  more  dissolves,  the  layer  of  nitrile 
separated  from  the  aqueous  solution  and  finally  redistilled 
over  phosphorus  pentoxide.  It  forms  a  colourless  liquid 
boiling  at  82°.  The  yield  is  about  95  per  cent. 

2.  FROM  THE  HALOGEN  COMPOUNDS 

This  method  is  confined  to  compounds  containing 
aliphatic  halogen  atoms,  and  consists  in  treating 
them  with  potassium  cyanide.  Occasionally  the  re- 
action is  carried  out  in  aqueous  solution,  but  as  a  rule 
alcohol  is  used  as  a  solvent.  Although  in  some  cases 
the  exchange  takes  place  at  the  ordinary  temperature, 
it  is  usually  necessary  to  boil  the  mixture  under  a 
reflux  condenser  for  some  time  or,  in  more  obstinate 
cases,  to  heat  under  pressure. 

PREPARATION  OF  ETHYLENE  CYANIDE  (SUCCINO- 
NITRILE)  (CHgCN.CHjsCN).1  One  hundred  grammes  of 
ethylene  bromide  are  dissolved  in  150  c.c.  of  alcohol,  and  the 
mixture  boiled  under  a  reflux  condenser.  A  cold,  concentrated, 
aqueous  solution  of  670  grm.  of  potassium  cyanide  is  then 
run  in  drop  by  drop  during  two  hours.  After  cooling,  the 
liquid  is  filtered  or  decanted  from  the  precipitated  potassium 
bromide  and  evaporated  on  the  water-bath  in  vacua.  The 
residue  is  taken  up  with  alcohol,  again  evaporated  in  vacuo 
on  the  water-bath,  and  the  residue  fractionated.  The  ethylene 
cyanide  forms  a  colourless  liquid  which  boils  at  147°  at  10  mm. 
The  yield  is  70  to  80  per  cent. 

In  all  cases  where  nitriles  are  being  prepared  from 
halogen  compounds  and  potassium  cyanide  by  double 
decomposition,  the  potassium  halide  formed  during 
the  reaction  tends  to  form  a  coating  round  the  potas- 
sium cyanide,  and  thus  prevent  further  action.  In 
order  to  avoid  this,  the  cyanide  is  added  very  slowly  as 
a  concentrated  aqueous  solution,  or  in  the  form  of  a 
very  fine  powder.  In  the  preparation  of  malonic 
ester  (p.  154),  cyanacetic  acid  is  formed  as  an  inter- 
mediate product  although  not  isolated.  Instead  of 
the  halogen  compound  the  sulphate  can  be  used, 
i  Bl.  [2]  50,  214. 


THE  NITRILES  OR  CYANIDES  187 

PREPARATION  OF  ACETONITRILE  (CH3CN).i  One 
gramme-molecule  (65  grm.)  of  powdered  potassium  cyanide  is 
dissolved  as  far  as  possible  in  50  to  60  c.c.  of  water,  and  to  the 
cold  solution  one  molecule  (126  grm.)  of  dimethyl  sulphate  is 
added  in  three  portions,  the  whole  being  vigorously  shaken 
and  cooled  under  the  tap  after  each  addition.  (N.B.  As 
dimethyl  sulphate  is  very  poisonous,  great  care  must  be 
taken  to  avoid  inhaling  any  of  its  vapour  (see  p.  183).  The 
milky  liquid  thus  obtained  is  then  distilled  from  the  water- 
bath  until  the  temperature  reaches  82°.  The  contents  of  the 
flask  (which  must  be  a  large  one  owing  to  frothing)  are  then 
cooled,  another  65  grm.  of  potassium  cyanide  added  slowly, 
and  the  whole  very  cautiously  distilled  from  the  water-bath. 
A  violent  reaction  sets  in,  and  when  this  has  modified  the  dis- 
tillation is  continued  until  the  contents  of  the  flask  become 
solid  and  nothing  more  passes  over.  The  acetonitrile  is 
purified  as  described  on  p.  185.  The  yield  is  almost  quanti- 
tative. 

3.     FROM  THE  DIAZO-COMPOUNDS 

This  is  the  method  most  frequently  used  in  pre- 
paring aromatic  nitriles.  The  exchange  can  be  brought 
about  in  two  ways  :  (a)  according  to  Sandmeyer  the 
diazo-solution  is  slowly  run  into  hot  potassium  cuprous 
cyanide  solution,  and  the  whole  then  heated  on  the 
water-bath  until  no  more  nitrogen  is  evolved  ;  or  (b) 
according  to  Gattermann 2  the  diazo-solution  is  treated 
with  sulphuric  acid  and  potassium  cyanide,  and  copper 
powder  then  added,  the  details  of  the  method  being 
exactly  similar  to  those  given  on  p.  76  for  iodo- 
benzene  and  on  p.  77  for  bromobenzene,  with  the 
exception,  of  course,  that  the  iodide  or  bromide  is 
replaced  by  an  equivalent  amount  of  cyanide. 

PREPARATION  OF  BENZONITRILE  (C6H5CN).3 
A  solution  of  potassium  cuprous  cyanide,  2CuCN.KCN,  is 
prepared  by  adding  28  grm.  of  potassium  cyanide  to  a  hot 
solution  of  25  grm.  of  crystallised  copper  sulphate  in  150  c.c. 
of  water,  the  whole  being  heated  until  the  precipitate  at  first 
formed  has  redissolved.  (N.B.  As  cyanogen  is  evolved,  this 

i  B.  40,  3215.  2  B.  23,  1218.  3  B.  17,  2653. 


1 88      PREPARATION  OF  ORGANIC  COMPOUNDS 

reaction  must  be  carried  out  in  an  efficient  draught  chamber.) 
The  solution  thus  obtained  is  heated  to  90°  under  a  reflux 
condenser,  and  a  solution  obtained  by  diazotising  9-3  grm.  of 
aniline  in  the  usual  way  (p.  238),  slowly  run  in,  the  whole  being 
well  shaken  at  frequent  intervals.  When  all  the  diazo-chloride 
has  been  added,  the  whole  is  heated  on  the  water-bath  until 
no  more  nitrogen  is  evolved,  and  then  distilled  in  steam. 
The  distillate  is  extracted  with  ether,  the  ethereal  solution 
washed  with  dilute  caustic  soda  and  dilute  sulphuric  acid, 
dried  with  calcium  chloride,  and  then  fractionated.  The 
benzonitrile  passes  over  as  a  colourless  oil  boiling  at  191°, 
and  smelling  rather  like  nitrobenzene.  The  yield  is  about 
60  per  cent. 

4.  BY  THE  ADDITION   OF   HYDROCYANIC  ACID 
TO  ALDEHYDES  AND  KETONES 

This  reaction  leads  to  oxy-nitriles  (cyanhydrins) : 

H  H 

R.C/         +  HCN  =  R.C/-CN 
X0  \OH 

and  is  best  carried  out  by  acting  on  the  bisulphite 
compounds  with  potassium  cyanide.1 

PREPARATION  OF  MANDELONITRILE  (C6H5.CHOH.CN)  .2 
Fifteen  grammes  of  benzaldehyde  are  shaken  with  50  c.c.  of 
saturated  sodium  bisulphite  solution.  After  standing  for  some 
time  the  crystalline  bisulphite  compound  is  filtered  off,  washed, 
first  with  a  little  cold  water  and  then  with  alcohol  and  ether. 
The  crystals  are  ground  up  to  a  thin  meal  with  water,  a  cold, 
concentrated,  aqueous  solution  of  potassium  cyanide  (12  grm.) 
added,  and  the  whole  well  shaken.  The  nitrile  separates 
out  as  an  oil  and  is  collected  and  washed  with  water.  The 
yield  is  almost  theoretical. 

PREPARATION      OF      ACETONE     CYANHYDRIN3 

(Me  2C  (OH)  CN).  Acetone  (one  molecule)  is  shaken  with  saturated 
sodium  bisulphite  solution  (one  molecule),  and,  after  cooling, 
a  cold  saturated  solution  of  potassium  cyanide  (ij  molecules) 
is  slowly  added.  The  crystalline  bisulphite  compound  soon 

1  B.  39,  1224  ;    D.R.P.  85,230. 

2  Loc.  cit. 

3  B.  39,  1225,  1857;   R.  28,  10. 


THE  NITRILES  OR  CYANIDES  189 

passes  into  solution  and  is  replaced  by  a  fluorescent  oil.  This 
is  extracted  several  times  with  ether,  the  ethereal  extracts 
shaken  with  saturated  bisulphite  solution  (to  remove  acetone) 
and  then  washed  with  saturated  salt  solution.  The  ether  is 
evaporated,  and  the  residual  oil  dried  in  a  vacuum  desiccator 
over  concentrated  sulphuric  acid.  Pure  acetone  cyanhydrin 
forms  a  colourless,  odourless  liquid  which  boils  at  82°  at  23  mm. 
As  obtained  above  it  is  usually  of  a  yellow  colour.  The  yield 
is  96  per  cent. 

Strecker1  showed    that    aldehyde-ammonias    react 
with   hydrocyanic   acid   to   give   amino-nitriles  : 

H  ^ 


R.C^-OH  +  HCN  =  R.C^CN  +  H2O 
XNH2  \NH2 

Tiemann2  found  that  the  two  steps  of  the  synthesis 
could  be  carried  out  in  the  reverse  order  : 


R.C^CN  +  NH3  -  R.C^-CN 
\OH  \NH 


Both  these  methods,  however,  suffer  from  the  dis- 
advantage of  necessitating  the  use  of  concentrated 
hydrocyanic  acid.  This  can  be  avoided  and  both 
steps  carried  out  in  one  operation  by  treating  the 
aldehyde  or  ketone  with  ammonium  cyanide  3  or  an 
equimolecular  mixture  of  potassium  cyanide  and 
ammonium  chloride.  The  condensation  is  usually 
carried  out  in  aqueous  or  aqueous  alcoholic  solu- 
tion. A  very  important  modification  of  this  method 
is  due  to  Bucherer4  and  Kncevenagel.6  They  found 

1  A.  75,  27  ;  176,  341  ;  211,  359;  B.  37,  1809. 

2  B.  13,  381.  3  B.  39,  1722. 

4  D,R,P,  157,710,  157,909,  158,090,  158,346;    B.  39,  989; 
2796,  5  6.37,4059,4073,4087, 


igo      PREPARATION  OF  ORGANIC  COMPOUNDS 

that  secondary  amino-nitriles  of  the  general  formula 

/CN 
RR'C\  ,  where  R  is  an  alkyl  or  aryl  group, 

XNHAr 

R'  an  alkyl  or  aryl  group  or  a  hydrogen  atom,  and  Ar 
an  aryl  group,  are  produced  when  aldehydes  or  ketones 
are  acted  upon  by  primary  aromatic  amines  and  potas- 
sium cyanide.  The  reaction  takes  place  with  greater 
ease  if  the  aldehyde  or  ketone  is  first  converted  into  its 
bisulphite  compound  by  treatment  with  sodium 
bisulphite  : 


R  .COH    +  KCN  +  ArNH2  =  R  .C-NHAr  +  KNaSO3  +H2O. 
\SO3Na  XCN 

PREPARATION  OF  o.-  CARBOXYPHENYL  -  AMINO  - 
AGETONITRILE,  C6H4^™(^2CN.  (a)i  Seven  grammes  of 

finely  powdered  potassium  cyanide  and  14  grm.  of  finely 
powdered  anthranilic  acid  are  suspended  in  50  c.c.  of  ether 
or  benzene  in  a  flask  fitted  with  a  reflux  condenser.  The 
whole  is  well  cooled  with  ice  or  a  freezing  mixture,  and  7-5 
c.c.  of  technical,  40  per  cent,  formaldehyde  added  slowly.  A 
brisk  reaction  sets  in  and  two  layers  are  formed,  the  lower  of 
which  solidifies  on  cooling  to  a  mass  of  crystals  of  the  potas- 
sium salt  of  the  required  acid.  This  is  collected,  dissolved 
in  water,  and  acidified  with  acetic  or  hydrochloric  acid.  The 
free  acid  separates  out  and  is  filtered  off,  washed  with  cold 
water,  and  recrystallised.  It  separates  from  alcohol  (3  parts) 
in  glittering  leaflets,  and  from  benzene  or  chloroform  in  long 
needles.  M.P.  i8i°-i83°.  Yield  almost  quantitative. 

(fr)  2  Twenty  cubic  centimetres  of  technical,  40  per  cent. 
sodium  bisulphite  solution  and  7-5  c.c.  of  technical,  40  per 
cent,  formaldehyde  are  mixed,  and  the  mixture  warmed  to 
6o°-7o°  until  the  smell  of  formaldehyde  has  vanished  (about 
20  minutes).  A  solution  of  14  grm.  of  anthranilic  acid  in 
exactly  the  equivalent  amount  of  concentrated  caustic  soda 
is  then  added,  and  the  whole  heated  on  the  water  -bath  until 
no  more  anthranilic  acid  is  present  (about  45  minutes).  The 

*  D.R.P.  157,710;  B.  39,  989;    J-pr.  [2]  63,  392. 
1  D.R.P.  157,909;  B.  39,  2807. 


THE  NITRILES  OR  CYANIDES  191 

reaction  is  followed  by  withdrawing  a  sample  from  time  to 
time,  acidifying  it  with  excess  of  acetic  acid,  and  adding  a  few 
drops  of  sodium  nitrite  to  the  well-cooled  mixture.  Anthranilic 
acid,  if  still  present,  is  thus  converted  into  a  diazo-salt,  which 
when  poured  into  an  alkaline  solution  of  R-salt  gives  a  red 
azo-colour.  When  a  sample  thus  tested  gives  only  a  very 
slight  coloration,  a  solution  of  7  grm.  of  potassium  cyanide 
in  25  c.c.  of  water  is  added,  and  the  whole  heated  to  7O°-8o° 
for  20  minutes.  After  cooling,  the  whole  is  made  strongly 
acid  with  concentrated  acetic  acid  and  the  nitrile  filtered  off 
and  purified  as  before.  Yield  almost  quantitative. 

/OH 


,„.,,*,.-          rVr  _  r  -R  [i]NH.CHt.OSO,Na 

U6±l4[2]COOH  "*     \  2  =  ^8±l4[2]COOH 

\O.SO2Na 

[i]NH.CH2.O.S02Na  [i]NH.CH2.CN 

C«H4[2]COOH  CeH4[2]COOH 

The  above  synthesis  is  of  considerable  importance 
as  the  acid  obtained  is  the  nitrile  of  phenylglycine-o.- 
carboxylic  acid,  into  which  it  passes  on  hydrolysis 
(boiling  with  hydrochloric  acid).  Phenylglycine-o.- 
carboxylic  acid,  of  course,  is  important  as  it  gives 
indigo  on  fusion  with  alkalis. 

5.  BY  THE  ADDITION   OF   HYDROCYANIC   ACID 
TO  THE  QUINONES 

The  quinones  readily  react  with  two  molecules  of 
hydrocyanic  acid,  but  in  a  different  way  from  the  ketones, 
the  product  being  a  2.3-dinitrilo-hydroquinone  : 

O  OH  OH 


/\ 


2 


+  2HCN      — 


\~-CN 


j— CN 


\/ 

II  I 

O  OH  OH 

A  molecule  of  the  quinone  is  simultaneously  reduced 
to  hydroquinone. 


192      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION     OF     DICYANO-HYDROQUINONE 

(HO)2C6H2(CN)2.1  Twenty  grammes  of  />.-benzoquinone  are 
dissolved  in  60  c.c.  of  alcohol,  and  a  cold  mixture  of  25  c.c. 
of  concentrated  sulphuric  acid  and  50  c.c.  of  alcohol  added. 
The  mixture  is  well  cooled,  and  a  concentrated  solution  of 
potassium  cyanide  slowly  run  in  until  a  green  fluorescence 
appears  and  the  liquid  reacts  alkaline.  The  whole  is  then 
acidified  with  sulphuric  acid  and  the  alcohol  removed  by 
distillation  in  vacuo  from  the  water-bath.  The  residue  is 
washed  with  water,  and  then  recrystallised  from  hot  water 
with  the  addition  of  animal  charcoal.  It  crystallises  in  pale 
yellow  leaflets  which  contain  two  molecules  of  water.  On 
heating,  it  decolorises  at  about  230°.  Its  neutral  solution 
fluoresces  blue,  its  acid  solution  violet,  and  its  alkaline  solution 
green. 

1  B.  33,  675;  D.R.P.  117,005. 


CHAPTER  IX 

THE  NITROSO-  (AND  *so-NITROSO-)  AND 
NITRO-COMPOUNDS 

THE  NITROSO-COMPOUNDS 

THE  nitroso-compounds  are  obtained  : 

i.  BY  THE  OXIDATION  OF  THE  ALIPHATIC 
AMINES  (R3C.NH2)  OR  OF  THE  AROMATIC 
AMINES  (ArNH2). 

The  oxidising  agent  chiefly  used  is  monopersulphuric 
acid  (Caro's  acid).  This  is  prepared  from  potassium  or 
ammonium  persulphate  and  sulphuric  acid  as  follows  : 

Eighteen  parts  of  finely  powdered  potassium  per- 
sulphate, or  an  equivalent  amount  of  the  ammonium 
salt,  are  slowly  added  (during  an  hour)  to  20  parts  of 
cold  concentrated  sulphuric  acid,  the  whole  being  well 
stirred,  and  the  stirring  continued  for  half  an  hour 
after  the  whole  of  the  persulphate  has  been  added.  Care 
must  be  taken  not  to  allow  any  rise  in  temperature. 
The  whole  is  then  slowly  poured  into  80  to  100  parts 
of  ice-water  and  either  directly  used  or  it  is  first 
neutralised  with  anhydrous  sodium  carbonate.  The 
solution  must  not  react  alkaline.  If  it  is  desired  to 
preserve  the  reagent,  the  concentrated  acid  is  not 
poured  into  water,  but  is  rubbed  up  to  a  dry  powder 
with  60  grm.  of  potassium  sulphate  and  then  kept  in 
well-stoppered  bottles.  It  is,  however,  best  to  prepare 
the  reagent  directly  before  use.  The  active  oxygen 
in  the  solution  is  estimated  either  by  adding  a  known 
excess  of  ferrous  sulphate  and  then  titrating  the 
excess  of  ferrous  salt  with  permanganate,  or  excess  of 

193  13 


194      PREPARATION  OF  ORGANIC  COMPOUNDS 

oxalic  acid  is  added  and  the  excess  titrated  in  the 
presence  of  silver  sulphate  :  * 

K2S208  +  H2S04  +  H20  =  K2S04  +  H2SO4  +  H2SO5. 

PREPARATION  OF  NITROSOBENZENE  (C6H6NO).2 
Three  grammes  of  aniline  dissolved  in  150  c.c.  of  water  are 
added  to  the  calculated  volume  of  a  neutral  solution  of  Caro's 
acid,  prepared  as  described  above.  The  nitrosobenzene 
separates  out,  and  is  collected,  washed  with  a  little  water,  and 
then  steam-distilled.  Colourless  or  yellow  crystals  melting  at 
68°.  It  is  green  when  fused  or  dissolved. 

PREPARATION  OF  w.-NITRO-NITROSOBENZENE  (C6H4 
(NO)NO2)  .3  Twenty  grammes  of  finely  powdered  m.-nitraniline 
are  suspended  in  1500  c.c.  cold  water.  A  neutralised  solution 
of  Caro's  acid,  prepared  as  above  and  containing  4-7  grm.  of 
active  oxygen  (about  90  grm.  of  persulphate  will  be  required), 
is  then  added  and  the  whole  well  stirred  for  half  an  hour. 
The  precipitate  is  then  collected,  washed,  and  steam-distilled 
in  small  portions  (not  more  than  3  grm.  at  a  time  as  otherwise 
decomposition  will  take  place).  It  forms  colourless  needles 
melting  at  90°.  The  yield  is  about  80  per  cent. 

2.  BY  THE  OXIDATION  OF  THE  HYDROXYL- 
AMINES. 

The  aliphatic  hydroxylamines  are  best  oxidised  with 
potassium  bichromate  and  sulphuric  acid,  whereas  in 
the  aromatic  series  ferric  chloride  is  the  best  oxidising 
agent. 

PREPARATION  OF  m.-DINITROSOBENZENE  (C6H4 
(NO)2).4  Five  grammes  of  ra.-dinitrobenzene  are  dissolved 
in  50  c.c.  of  alcohol  containing  6  c.c.  of  glacial  acetic  acid. 
Two  grammes  of  zinc  dust  are  then  slowly  added,  the  tempera- 
ture being  kept  below  o°  by  means  of  a  freezing  mixture. 
When  the  greater  part  of  the  zinc  has  gone  into  solution, 
too  c.c.  of  water  and  then  200  c.c.  of  a  10  per  cent,  ferric 

1  B.  38,  3965- 

2  D.R.P.  105,875,  110,249,  110,575,  110,578. 

3  B.  36,  3800.    "  4  B.  38,  1899. 


THE  NITROSO-  AND  NITRO-COMPOUNDS       195 

chloride  solution  are  added,  and  the  whole  at  once  steam 
distilled.  The  first  20  c.c.  of  distillate  are  collected,  and  on 
standing  soon  precipitate  a  yellow  powder,  melting  at  146°  to  a 
green  liquid. 

C6H4(N02)2  +  8H  =  C6H4(NHOH)2  +  2H2O. 
C6H4(NHOH)2  +  20  =  C6H4(NO)2  +  2H2O. 

3.  BY   THE    ADDITION   OF   N2O3    OR   NOC1. 

Nitrosyl  chloride  and  nitrogen  trioxide  both  add  on 
to  double  bonds,  the  former  giving  a  chloronitroso- 
compound  and  the  latter  a  nitrosite,  e.g.  Me2C(ONO) . 
CMeHNO. 

PREPARATION  OF  TRIMETHYLETHYLENE  NITROSITE 

(Me3C(ONO)  CMeHNO).1  Twenty  grammes  of  trimethyl- 
ethylene  («so-amylene)  are  dissolved  in  60  c.c.  of  ether,  and  the 
whole  cooled  to  o°.  A  stream  of  moist  nitrogen  trioxide 
(obtained  by  the  action  of  80  c.c.  of  nitric  acid  of  density  1-43 
on  1 20  grm.  of  arsenious  acid)  is  then  led  into  the  solution. 
The  gas  is  absorbed  with  considerable  evolution  of  heat,  and 
care  must  be  taken  that  the  temperature  does  not  rise  above 
10°.  When  no  more  gas  is  absorbed  and  the  smell  of  trimethyl- 
ethylene  has  practically  vanished,  the  reaction  is  stopped, 
and  excess  of  nitrous  acid  removed  from  the  ethereal  solution 
by  washing  ten  or  twelve  times  with  water.  The  ethereal 
solution,  which  should  now  have  a  pure  blue  and  not  a  greenish 
blue  colour,  is  dried  with  sodium  sulphate,  and  the  ether 
removed  by  distillation  from  as  cool  a  water -bath  as  possible, 
the  flask  being  continually  shaken  during  the  distillation.  A 
blue  liquid  remains  which  is  freed  from  traces  of  ether  and 
trimethylethylene  by  placing  in  a  vacuum  desiccator  over 
solid  potash  and  sulphuric  acid.  The  yield  is  35  grm.,  but 
the  substance  is  not  quite  pure.  It  is  purified  by  allowing  it 
to  stand  at  the  room  temperature  for  a  day  or  two,  when  it 
changes  into  a  crystalline  polymer  (colourless  needles).  This 
is  washed  with  ether  and  then  depolymerised  by  heating  for 
a  short  time  to  75°. 

4.  THE   NITROSO-PHENOLS  (which   are   identical 
with  the  quinone  monoximes)   and  the  AROMATIC 

i  B.  35,  2327,  2978,  4120  ;   36,  1765. 


196     PREPARATION  OF  ORGANIC  COMPOUNDS 

NITROSO-TERTIARY  AMINES  are  obtained  by  the 
action  of  nitrous  acid  on  the  phenols  or  on  the  tertiary 
bases.  The  nitroso-group  takes  the  para-  position  in 
both  cases.  Monohydric  phenols  only  give  mono- 
nitroso-compounds,  but  dihydric  phenols  give  dinitroso- 
compounds.  The  action  of  nitrous  acid  on  a-naphthol 
leads  to  a  mixture  of  a-  and  /5-nitroso-a-naphthols, 
the  nitroso-group  entering  the  o.-  and  p.-  positions. 
/3-Naphthol  gives  only  i-nitroso-2-naphthol. 

The  nitroso-phenols  can  also  be  obtained  by  heating 
the  nitroso-tertiary  bases  with  alkali. 

PREPARATION  OF  £.-NITROSOPHENOL  (NOC6H4OH). 
(a)  1  Ten  grammes  of  phenol  and  40  grin,  of  potassium  nitrite 
are  dissolved  in  two  litres  of  ice- water,  and  then  25  grm.  of 
glacial  acetic  acid  diluted  with  ten  volumes  of  water  slowly 
added  with  continual  stirring.  The  whole  is  allowed  to  stand 
over-night,  and  then  filtered  and  extracted  with  ether.  On 
shaking  the  ethereal  extract  with  concentrated  caustic  soda 
solution  brown  needles  of  sodium  nitrosophenate  separate. 
These  are  collected  and  spread  on  a  porous  plate  until  the 
whole  of  the  adhering  liquid  has  been  absorbed.  They  are 
then  dissolved  in  a  little  water  and  decomposed  with  dilute 
sulphuric  acid.  The  precipitated  nitroso-phenol  is  collected, 
washed,  dissolved  as  rapidly  as  possible  in  a  little  boiling 
water,  the  solution  filtered  hot,  cooled,  and  finally  extracted 
with  ether.  On  removing  the  ether  by  distillation,  nitroso- 
phenol  is  left  in  a  pure  state.  Rhombic  crystals  melting  at 
125°.  The  yield  is  almost  quantitative. 

(b)  2  One  hundred  grammes  of  3  per  cent,  caustic  soda 
solution  are  boiled  under  a  reflux  condenser,  and  2  grm. 
of  ^.-nitrosodimethylaniline  hydrochloride  added  little  by 
little,  time  being  allowed  after  each  addition  for  practically 
all  the  oil  which  separates  to  disappear.  After  all  the  p.- 
nitrosodimethylaniline  has  been  added,  the  boiling  is 
continued  until  the  solution  becomes  reddish  yellow  in 
colour.  It  is  then  cooled  in  ice,  made  faintly  acid  with 
dilute  sulphuric  acid  and  extracted  with  ether.  On  evapo- 
rating the  ether  the  nitrosophenol  remains  as  a  mass  of 
crystals. 

The  nitrosophenol  obtained  by  these  two  methods  is  identical 

i  B.  7,  967  ;  A.  277,  85.  2  B.  7,  809. 


THE  NITROSO-  AND  NITRO-COMPOUNDS       197 

with  the  quinone  monoxime  obtained  by  boiling  quinone  with 
one  molecule  of  hydroxylamine  hydrochloride. 

PREPARATION  OF  2.4-DINITROSORESORCINOL  (Fast 
Green  O).1  Ten  grammes  of  resorcinol  are  dissolved  in  250 
c.c.  of  water  containing  n  grm.  of  concentrated  sulphuric 
acid.  Ice  is  then  added  until  the  temperature  has  fallen  to  o°. 
A  solution  of  13  grm.  of  sodium  nitrite  in  100  c.c.  of  water  is 
then  slowly  added  with  continual  stirring,  more  ice  being  added 
from  time  to  time  so  as  to  keep  the  temperature  below  8°. 
The  solution,  which  should  be  faintly  acid  in  reaction,  is 
allowed  to  stand  for  an  hour  and  then  filtered.  The  precipitate 
is  washed  with  ice-water  and  then  dried  on  a  porous  plate. 
Greyish  brown  powder.  Yield  18  grm.  It  dyes  cotton  or 
wool  green  on  an  iron  mordant. 

OH 


or 


NO  N.OH 


PREPARATION  OF  £.-NITROSO-DIMETHYLANILINE 
HYDROCHLORIDE  (NO .  C6H4NMe2HCl)  .2  One  hundred 
grammes  of  dimethylaniline  are  dissolved  in  350  c.c.  of  con- 
centrated hydrochloric  acid,  and  ice  added  to  the  solution 
until  the  temperature  falls  below  o°.  A  cold  concentrated 
solution  of  60  grm.  of  sodium  nitrite  is  then  slowly  run  in 
with  continual  stirring,  the  temperature  being  kept  below  8°. 
When  all  the  nitrite  has  been  added,  the  whole  is  allowed  to 
stand  for  an  hour  and  then  filtered,  and  the  precipitate  washed 
with  dilute  hydrochloric  acid  and  dried.  Yellow  needles 
melting  at  177°.  Yield  about  90  per  cent. 

5.  THE  NITROSAMINES.  The  nitrosamines  con- 
tain the  group  R2N.NO,  and  are  obtained  by  the 
action  of  nitrous  acid  on  the  secondary  amines. 

1  Schultz,  "  Chemie  des  Steinkoklenteers  "  (1901),  II.  242. 

2  B.  12,  523. 


198      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION      OF     DIPHENYL  -NITROSAMINE 

(CaH5)2N.NO.1  Thirty-four  grammes  of  diphenylamine  are 
dissolved  in  150  c.c.  of  warm  alcohol,  and  the  solution  then 
cooled  to  the  ordinary  temperature.  Sixteen  cubic  centi- 
metres of  pure  concentrated  hydrochloric  acid  are  added, 
and  then  a  solution  of  14  grm.  of  sodium  nitrite  in  250  c.c.  of 
water  is  slowly  run  in,  the  whole  being  well  stirred  and  cooled 
in  ice  or  a  freezing  mixture.  After  the  whole  of  the  nitrite 
has  been  added  the  solution  is  allowed  to  stand  for  one  hour 
in  a  freezing  mixture  and  then  filtered,  and  the  precipitate 
washed  with  a  large  quantity  of  cold  water.  It  is  finally 
recrystallised  from  alcohol  or  petroleum  ether  and  dried 
between  filter-paper.  Pale  yellow  leaflets  melting  at  165°. 
Yield  75  per  cent. 

6.  THE  wo-NITROSO  -  COMPOUNDS.  The  iso- 
nitroso  compounds  are  the  monoximes  of  the  a-diketones 
and  are  obtained  by  the  action  of  nitrous  acid  on  those 
ke  tones  which  contain  the  group  —  CH2  —  CO  —  . 

PREPARATION      OF     iso  -  NITROSOCAMPHOR,2 
,CO 

One  hundred  and  two  grammes  of  cam- 


=  NOH. 

phor  are  dissolved  in  500  c.c.  of  dry  ether,  and  15  grm.  of 
sodium  wire  added.  The  flask,  which  should  be  a  large  one, 
is  well  cooled  in  ice-water  or  a  freezing  mixture.  A  small 
quantity  of  amyl  nitrite  is  then  added,  when  the  solution 
becomes  yellow  and  some  frothing  takes  place.  Once  the 
reaction  has  started,  the  amyl  nitrite  (78  grm.  in  all  are  required) 
can  be  added  more  rapidly,  but  the  flask  must  be  kept  well 
cooled  and  must  be  vigorously  shaken  after  each  addition 
of  the  nitrite.  When  all  the  nitrite  has  been  added,  the  whole 
is  allowed  to  stand  for  an  hour,  when  part  of  the  sodium 
iso-nitrosocamphor  will  separate  out.  At  the  end  of  this  time 
the  whole  contents  of  the  flask  are  slowly  poured  into  ice-water 
(take  care  that  there  is  no  unchanged  sodium  left  !)  and  the 
ethereal  layer  removed.  The  reddish  yellow  aqueous  solution 
is  extracted  several  times  with  ether  in  order  to  remove  borneol 
and  unchanged  camphor,  and  is  then  freed  from  dissolved 
ether  by  blowing  air  through  it  for  a  short  time.  The  iso- 

*  B.  33,  1026.  2  A.  274,  73. 


THE  NITROSO-  AND  NITRO-COMPOUNDS       199 

nitrosocamphor  is  finally  thrown  down  by  adding  dilute 
acetic  acid  until  no  more  precipitation  takes  place.  The  yield 
is  about  40  grm.,  and  the  compound  is  usually  sufficiently 
pure  for  the  preparation  of  camphor  quinone  (p.  130).  It 
may  be  further  purified  by  recrystallising  several  times  from 
petroleum  ether  and  benzene,  or  from  dilute  methyl  alcohol. 
The  pure  compound  melts  at  152°-! 54°. 


THE  NITRO-COMPOUNDS 
THE  ALIPHATIC  NITRO-COMPOUNDS 

(a)  DIRECT  NITRATION.     Concentrated  nitric  acid 
usually  either  does  not  attack  or  completely  destroys 
fatty   hydrocarbons,  but    the    higher    paraffins    and 
naphthenes    can    be  nitrated    by  prolonged  heating 
with  a  20  per  cent,  acid  under  pressure.     The  yields, 
however,  are  poor,  owing  to  oxidation.     Dilute  nitric 
acid  also  nitrates  the  benzene  hydrocarbons  in  the  side- 
chain,  the  nucleus  being  unattacked.     According  to 
a   recent   patent,1  nitrophenyl-nitromethane   and  its 
derivatives   are   readily   obtained   by  heating   nitro- 
toluene,  &c.,  with  40  to  90  per  cent,  nitric  acid  in  open 
vessels. 

PREPARATION  OF  PHENYLNITROMETHANE  (o>- 
NITROTOLUENE)  (C6H5CH2NO2)  .2  Twenty  grammes  of 
toluene  and  120  c.c.  of  13  per  cent,  nitric  acid  are  heated  for 
five  hours  in  a  sealed  tube  to  io5°-io8°.  The  product  is 
made  alkaline  with  caustic  potash,  and  unchanged  toluene 
removed  by  extraction  with  ether.  The  alkaline  solution  of 
sodium  phenylnitromethane  (Ph .  CH  =  NO2Na)  is  then  decom- 
posed by  saturating  with  carbon  dioxide.  The  liberated 
nitro-compound  is  extracted  with  ether,  the  ethereal  solution 
dried  with  calcium  chloride,  and  the  ether  distilled  off  from 
the  water-bath.  The  residual  yellow  oil  is  fractionated  under 
reduced  pressure.  The  phenyl  nitromethane  passes  over  as  a 
colourless  liquid  boiling  at  141°  at  35  mm. 

(b)  BY     THE     REPLACEMENT     OF      HALOGEN. 
Methyl  iodide  when  treated  with  silver  nitrite  gives 

i  E.  P.  607611.  a  B.  28,  1861. 


200      PREPARATION  OF  ORGANIC  COMPOUNDS 

nitrome thane,  but  the  higher  alkyl  halides  give  a 
mixture  of  the  nitro -hydrocarbon  and  nitrous  ester, 
the  latter  in  increasing  quantity  as  the  molecular 
weight  of  the  alkyl  radical  increases.  When  sodium 
nitrite  acts  on  the  alkyl  halides,  only  nitrous  esters, 
R.ONO,  are  obtained,  but  with  halogen  fatty  acids 
the  nitro  -  acid  is  produced,  and  this  readily  loses 
carbon  dioxide  to  form  the  nitro -hydrocarbon,  e.g.  : 

NaNO2  H2O 

CH2ClCOONa  -*  CH2NO2 .  COONa  —  NaHCO3  +  CH3NO2. 

PREPARATION  OF  NITROMETHANE  (CH3NO2).i  Five 
hundred  grammes  of  chloracetic  acid  are  dissolved  in  i  litre 
of  water,  carefully  neutralised  with  solid  sodium  carbonate, 
and  300  grm.  of  sodium  nitrite  in  500  c.c.  of  water  added. 
About  300  c.c.  of  the  solution  thus  obtained  are  placed  in  a 
2-litre  flask  provided  with  a  condenser,  and  heated  to  boiling. 
The  rest  of  the  solution  is  then  slowly  run  in  from  a  tap  funnel 
at  such  a  rate  that  oily  drops  are  always  seen  in  the  condenser 
(about  2  J-  hours  will  be  required) .  The  liquid  in  the  flask  assumes 
a  dark  red  colour,  and  a  colourless  oil  collects  in  the  receiver, 
which  should  consist  of  an  apparatus  as  described  on  p.  25 
(if  this  is  not  used  the  receiver  must  be  changed  frequently), 
and  the  oil  separated  from  the  aqueous  part  of  the  distillate. 
The  distillation  should  be  continued  until  250  c.c.  of  liquid 
have  been  collected  after  no  more  oily  drops  are  visible  in  the 
condenser.  The  aqueous  part  of  the  distillate  is  then  redistilled 
with  the  addition  of  common  salt  (35  grm.  to  every  100  c.c.). 
The  distillation  is  carried  on  until  two-thirds  of  the  liquid  have 
passed  over,  the  oil  being  continually  separated  as  before.  The 
aqueous  part  of  the  distillate  is  then  again  distilled  with  salt, 
and  this  process  continued  until  no  more  oil  can  be  obtained. 
Finally  all  the  yields  of  oil  are  united,  dehydrated  with  calcium 
chloride,  and  distilled.  Practically  the  whole  passes  over  at 
101°.  Yield  about  25  per  cent. 

THE  AROMATIC  NITRO-COMPOUNDS 

The  only  method  of  any  practical  importance  for 
the  preparation  of  aromatic  nitro-compounds  is  direct 
nitration  with  nitric  acid.     Amino-compounds,  phenols, 
i  B.  42,  3438. 


THE  NITROSO-  AND  NITRO-COMPOUNDS       201 

&c.,  which  are  very  sensitive  to  oxidation,  must  first 
be  protected  by  replacing  one  of  the  amino-  or  phenolic 
hydrogen  atoms.  This  is  best  done  by  preparing  an 
ester  (of  the  phenol)  or  an  anilide  (see  p.  228).  The 
amino-compounds  can  also  be  converted  into  the 
benzylidene  derivative  by  means  of  benzaldehyde 
(see  pp.  115,  233). 

NITRIC  ACID  ALONE.  Concentrated  nitric  acid 
often  contains  nitrous  fumes  which  sometimes  have  a 
deleterious  action.  They  can  be  destroyed  by  heating 
the  acid  with  a  little  urea  : 

CO(NH2)2  +  2HN02  =  CO2  +  3H2O  +  2N2. 
This  treatment,  however,  is  not  usually  necessary. 

PREPARATION    OF    o.-    AND    /.-NITROPHENOL 

(C6H4(OH)NO2).  Fifty  grammes  of  phenol  are  slowly 
added  to  275  c.c.  of  nitric  acid  (D  =  i-n),the  whole  being 
well  cooled  with  water.  After  each  addition  of  phenol  the 
flask  must  be  well  shaken.  The  solution  becomes  very 
dark  in  colour  and  an  oily  mass  separates  out.  After  all 
the  phenol  has  been  added  the  whole  is  allowed  to  stand  for 
twelve  hours.  The  supernatant  acid  is  then  poured  off,  the 
residue  washed  several  times  by  decantation  and  then  steam- 
distilled.  o.-Nitrophenol  passes  over  in  the  pure  state  and 
solidifies  in  the  receiver  to  yellow  needles  melting  at  45°. 
Yield  15  to  20  grm.  The  residue  in  the  flask  is  boiled  with 
dilute  caustic  soda,  filtered,  the  filtrate  boiled  for  a  short 
time  with  animal  charcoal,  refiltered,  and  then  concentrated 
to  a  small  volume.  After  cooling,  concentrated  caustic  soda 
solution  is  added,  which  causes  the  sodium  salt  of  p.-mtro- 
phenol  to  separate  as  yellow  crystals.  These  are  filtered  off 
(use  glass-wool),  dissolved  in  cold  water,  the  solution  filtered, 
acidified  with  concentrated  hydrochloric  acid,  and  the  pre- 
cipitated p.-nitrophenol  recrystallised  from  boiling  water  to 
which  a  few  drops  of  concentrated  hydrochloric  acid  have 
been  added.  Colourless  needles  melting  at  114°.  Yield  about 
15 


NITRIC  ACID  AND  AN  ORGANIC  SOLVENT.  The 
solvents  used  may  be  divided  into  two  classes,  viz.  : 
(a)  solvents  immiscible  with  nitric  acid  ;  (b)  solvents 


202      PREPARATION  OF  ORGANIC  COMPOUNDS 

miscible  with  nitric  acid.  Examples  of  the  former 
are  carbon  tetrachloride,  paraffins,  and  with  dilute 
nitric  acid,  benzene.  During  the  nitration  the  solu- 
tion must  be  kept  violently  agitated,  and  the  nitric 
acid  is  always  added  to  the  solution  of  the  substance 
to  be  nitrated.  The  method  is  seldom  employed, 
but  is  sometimes  useful  with  substances  which  are 
readily  oxidised,  as  the  solvent  to  some  extent  protects 
the  nitrated  compound  from  further  action  of  the  acid. 
As  solvents  of  the  second  class  glacial  acetic  acid  and 
sulphuric  acid  are  by  far  the  most  common.  The 
latter  is  dealt  with  in  the  next  section  under  "mixed 
acids." 

PREPARATION      OF      s.s'-DINITROCARBAZOLE.1 

Twenty  grammes  of  carbazole  are  dissolved  in  100  c.c.  of  glacial 
acetic  acid,  and  the  solution  then  heated  to  80°.  At  this 
temperature  26  grm.  of  nitric  acid  (D  =  1-38)  are  slowly 
added,  the  whole  being  well  stirred.  When  all  the  acid  has 
been  added  the  solution  is  heated  to  100°  for  about  half  an 
hour  and  then  allowed  to  cool.  The  dinitro  carbazole  separates 
out  and  is  collected. 


NO, 


N02 


MIXED  ACIDS.  A  mixture  of  nitric  and  concen- 
trated sulphuric  acids  is  the  most  commonly  employed 
nitrating  agent.  The  proportions  in  which  the  acids 
are  used  vary  to  a  considerable  extent,  but  i  part 
of  nitric  acid  (D  =  1-4)  to  about  i£  parts  of  concen- 
trated sulphuric  acid  is  an  average  proportion.  Excel- 
lent results  are  sometimes  obtained  by  adding  the 
nitric  acid  in  the  form  of  one  of  its  salts,  usually  as 
potassium  nitrate.  Considerable  heat  is  evolved  when 
nitric  acid  is  added  to  concentrated  sulphuric  acid,  and 
the  former  must,  therefore,  be  added  slowly  to  the 
latter. 

1  D.R.P.  46,438,  128,853. 


THE  NITROSO-  AND  NITRO-COMPOUNDS        203 

PREPARATION  OF  NITROBENZENE  (C6H5NO2).  Sixty- 
three  grammes  of  nitric  acid  (D  =  1-4)  are  slowly  added  to 
50  c.c.  of  concentrated  sulphuric  acid,  and  the  mixture,  after 
cooling,  slowly  run  into  50  grm.  of  benzene.  During  this 
addition  the  flask  must  be  well  shaken  and  the  temperature 
must  not  exceed  25°.  When  all  the  acid  has  been  added  and 
no  further  rise  in  temperature  takes  place,  the  whole  is 
heated  on  the  water-bath  to  60°  for  one  hour  under  a  reflux 
condenser.  After  cooling,  the  upper  layer  of  nitrobenzene 
is  separated,  well  washed,  first  with  water,  then  with  dilute 
sodium  carbonate,  and  finally  again  with  water.  It  is  then 
dehydrated  over  calcium  chloride  and  distilled.  A  little 
unchanged  benzene  passes  over  first,  but  the  greater  part  of 
the  liquid  passes  over  at  2o6°-2O7°.  It  forms  a  pale  yellow 
oil  with  a  smell  of  bitter  almonds. 

PREPARATION  OF  m.-DINITROBENZENE  (C6H4(NO2)2). 
Twenty  grammes  of  nitrobenzene  are  slowly  added  to  a  mixture 
of  20  c.c.  of  fuming  nitric  acid  (D  =  1-5)  and  20  c.c.  of  con- 
centrated sulphuric  acid.  The  whole  is  then  heated  on  the 
water-bath  until  a  completely  hard  and  solid  yellow  precipi- 
tate is  obtained  on  adding  a  few  drops  to  a  test-tube  of  cold 
water.  Without  cooling,  the  whole  is  then  poured  into  a  large 
volume  of  cold  water,  the  precipitate  filtered  off,  washed,  and 
recrystallised  from  alcohol.  Long  colourless  needles  melting 
at  90°.  Yield  almost  quantitative. 

PREPARATION  OF  a -NITRON  APHTHALENE  (C10H7NO2). 
Fifty  grammes  of  finely  powdered  naphthalene  are  slowly 
added  to  a  mixture  of  30  c.c.  of  nitric  acid  (D  =  1-4)  and 
30  c.c.  of  concentrated  sulphuric  acid,  the  temperature  being 
kept  at  40°-5o°.  When  all  the  naphthalene  has  been  added, 
the  whole  is  heated  to  60°  and  then  poured  into  cold  water. 
The  precipitated  nitronaphthalene  is  collected,  boiled  up  with 
water,  and  the  water  poured  off  from  the  molten  substance. 
It  is  then  steam-distilled  until  no  more  unchanged  naphthalene 
passes  over.  The  residue  while  still  hot  is  poured  on  to 
crushed  ice  or  into  a  large  bulk  of  cold  water.  The  nitro- 
naphthalene is  filtered  off  and  recrystallised  from  spirit. 
Long  yellow  needles.  M.P.  61°.  Yield  about  90  per  cent. 

PREPARATION    OF    2-NITROBENZIDINE     (NH2[4]C6H4 
[i][i']C6H4[2']NO2[4']NH2).i     Twenty-eight  grammes  of  pure 
1  B.  23,  796. 


204      PREPARATION  OF  ORGANIC  COMPOUNDS 

benzidine  sulphate  are  added  to  300  grm.  of  pure  concentrated 
sulphuric  acid  and  the  whole  well  stirred.  If  necessary, 
solution  is  completed  by  warming  to  5o°-6o°.  The  solution 
is  then  cooled  to  io°-2O°  (the  temperature  must  not  fall 
below  10°).  At  this  temperature  10  grm.  of  potassium 
nitrate  are  slowly  added,  and  the  stirring  continued  for  some 
hours.  The  solution  is  poured  into  a  litre  of  cold  water,  and 
the  precipitated  nitrobenzidine  sulphate  filtered  off  and  re- 
crystallised  from  boiling  water  in  the  presence  of  animal  char- 
coal. By  using  double  the  amount  of  potassium  nitrate  2-2'- 
dinitrobenzidine  is  obtained. 

PREPARATION  OF  m.-NITROBENZOIC  ACID  (C6H4[i] 
COOH[3]NO2).  Fifty  grammes  of  benzoic  acid,  which  have 
been  dehydrated  by  fusing,  are  intimately  mixed  with  100 
grm.  of  potassium  nitrate.  The  mixture  is  then  slowly 
added  to  150  grm.  of  concentrated  sulphuric  acid,  the  whole 
being  well  stirred.  When  all  has  been  added,  the  mixture  is 
gently  warmed  until  the  nitrated  acid  separates  out  as  an  oily 
layer.  This  solidifies  on  cooling  and  is  removed  and  roughly 
purified  by  twice  melting  it  with  water.  It  is  then  steam-dis- 
tilled to  remove  unchanged  benzoic  acid,  and  the  residue 
dissolved  in  about  twenty  times  its  weight  of  boiling  water. 
The  solution  is  made  slightly  alkaline  with  hot  concentrated 
baryta  water  and  then  cooled.  The  barium  salt  of  the  meta- 
nitro-acid  separates  out,  the  ortho-  and  para-  acids  remaining 
in  solution.  It  is  collected,  washed,  and  decomposed  with 
hydrochloric  acid.  The  precipitated  m.-nitrobenzoic  acid  is 
filtered  off,  washed,  and  dissolved  in  sodium  carbonate  solution. 
The  solution  is  freed  from  suspended  barium  sulphate  by 
filtration,  the  w.-nitrobenzoic  acid  precipitated  by  hydro- 
chloric acid,  and  recrystallised  from  water.  It  melts  at 
141°.  Yield  45  per  cent. 

PREPARATION     OF      I-CHLOR-2.4-DINITROBENZENE. 

Chlorobenzene  is  boiled  with  excess  of  concentrated  nitric 
acid  (D  =  i -5)  or  is  heated  with  mixed  acids  until  a  sample 
gives  a  completely  solid  precipitated  with  water.  The  whole 
is  then  poured  into  water  or  crushed  ice,  and  the  solid  collected, 
washed,  and  recrystallised  from  alcohol.  It  melts  at  38°. 

PREPARATION       OF       /.-NITRANILINE     (C6H4[i]NH2 
1     One  hundred  grammes  of  acetanilide  are  dissolved 
1  B.  17,  262. 


THE  NITROSO-  AND  NITRO-COMPOUNDS        205 

in  100  grm.  of  hot  glacial  acetic  acid,  and  the  solution,  after 
cooling,  mixed  with  400  grm.  of  concentrated  sulphuric  acid. 
The  whole  is  well  cooled  in  a  freezing  mixture,  and  a  cold 
mixture  of  59  grm.  of  nitric  acid  (D  =  1-48)  and  120  grm.  of 
concentrated  sulphuric  acid  slowly  run  in  with  stirring. 
After  standing  for  a  time  the  whole  is  poured  on  to  crushed 
ice,  the  precipitated  p.-nitroacetanilide  filtered  off,  washed, 
and  recrystallised  from  water  or  dilute  alcohol.  Yield  95  per 
cent.  M.P.  207°.  To  convert  this  into  ^.-nitraniline,  it  is 
boiled  under  a  reflux  condenser  with  2^-  parts  of  concentrated 
hydrochloric  acid  or  25  per  cent,  sulphuric  acid  until  the  whole 
dissolves.  The  solution  is  then  made  alkaline  with  caustic 
soda  or  ammonia,  and  on  cooling,  the  nitraniline  crystallises 
out.  It  is  filtered  off,  washed,  and  recrystallised  from  boiling 
water.  Yellow  needles.  M.P.  147°.  Yield  about  90  per  cent. 

PREPARATION  OF  NAPHTHOL  YELLOW  S.1   One 

hundred  grammes  of  a-naphthol  are  finely  powdered  and  slowly 
added  to  225  c.c.  of  concentrated  sulphuric  acid  at  100°  C. 
The  temperature  is  then  raised  to  120°,  and  kept  at  that  point 
for  three  to  four  hours.  The  mixture  is  poured  into  600  c.c. 
of  water  and  stirred  until  the  temperature  has  reached  30°. 
At  this  point  145  c.c.  of  concentrated  nitric  acid  are  slowly 
run  in,  care  being  taken  that  the  temperature  does  not  rise 
above  45°.  After  standing  for  a  time  the  free  acid  separates 
out  and  is  washed  with  saturated  salt  solution  until  free  from 
acid.  It  is  then  mixed  with  boiling  water,  and  potassium  car- 
bonate added  until  a  permanent  alkaline  reaction  is  obtained. 
The  potassium  salt  separates  out  on  cooling  and  is  filtered 
off.  It  forms  an  orange-yellow  powder  which  dyes  wool  or 
silk  from  an  acid  bath. 

OK 


K03S 


N02 
Naphthol  Yellow  S 

When  sulphonic  acids  are  nitrated  it  often  happens 
that  the  sulphonic  acid  group  is  replaced  by  the  nitro- 
group. 

1  Cain  and  Thorpe,  "  Synthetic  Dyestuffs,"  p.  226. 


206      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  PICRIC  ACID  (2.4.6-TRINITRO- 
PHENOL) .  Fifty  grammes  of  phenol  are  heated  with  an  equal 
weight  of  concentrated  sulphuric  acid  until  a  clear  solution 
of  phenol  sulphonic  acid  is  obtained.  After  cooling,  the 
solution  is  poured  into  half  its  volume  of  water,  well 
cooled,  and  then  slowly  run  into  140  c.c.  of  concentrated 
nitric  acid.  During  this  operation,  which  should  be  carried 
out  in  a  large  flask,  the  whole  must  be  well  cooled  and  shaken. 
Oxides  of  nitrogen  and  considerable  heat  are  evolved.  When 
all  the  phenol  sulphonic  acid  has  been  run  in,  53  c.c.  of  fuming 
nitric  acid  (D  =  1-5)  are  added,  and  the  whole  heated  on  the 
water-bath  for  two  hours.  On  cooling,  the  picric  acid  separates 
out  and,  after  dilution,  is  filtered  off,  washed  with  cold  water, 
and  recrystallised  from  boiling  water.  It  forms  long,  pale 
yellow  needles  which  melt  at  122°,  and  explode  violently  if 
suddenly  heated.  It  is  a  strong  acid,  about  as  strong  as 
hydrochloric  acid,  and  readily  forms  metallic  salts.  As 
these  are  exceedingly  explosive,  especially  the  salts  of  the 
heavy  metals,  care  should  be  taken  not  to  allow  picric  acid  to 
remain  in  contact  with  metallic  substances. 

ADDENDA 

THE  PICRATES.  Some  aromatic  organic  com- 
pounds, such  as  the  hydrocarbons  and  naphthols, 
readily  form  beautifully  crystalline  double  compounds 
with  picric  acid.  These  are  obtained  by  digesting  the 
hydrocarbon  on  the  water-bath  with  an  aqueous 
solution  of  picric  acid  saturated  at  the  ordinary  tem- 
perature, or  by  mixing  with  picric  acid  in  some  suitable 
organic  solvent,  such  as  alcohol.  They  often  form  a 
ready  means  of  separating  and  purifying  aromatic 
hydrocarbons,  and  have  also  been  used  for  their 
estimation.  Thus  benzene,  naphthalene,  &c.,  when 
digested  with  concentrated  aqueous  picric  acid  which 
has  previously  been  titrated  (baryta  water  and  phenol- 
phthalem  or  lacmoid),  are  quantitatively  converted 
into  the  picrate.  This  is  then  filtered  off,  and  the 
filtrate  re  titrated.  This  is  the  quantitative  estimation 
of  naphthalene  in  coal  gas.  The  picrates  are  also 
very  well  adapted  for  recognising  compounds  which 
form  them,  as  they  crystallise  well,  have  sharp  melting- 


THE  NITROSO-  AND  NITRO-COMPOUNDS       207 

points,  and  the  picric  acid  present  can  be  determined 
by  titration.     They  are  often  highly  coloured. 

NITRODIPHENYL  METHANES.  These  can  be  ob- 
tained by  condensing  two  molecules  of  an  aromatic 
nitro-hydrocarbon,  nitrophenol,  &c.,  with  one  molecule 
of  formaldehyde.  In  the  absence  of  other  groups,  the 
condensation  takes  place  in  the  meta-  position  to  the 
nitro-group.  The  condensation  is  best  brought  about 
with  concentrated  sulphuric  acid,  and  takes  place  at 
the  ordinary  temperature  or  on  gently  warming.  The 
reaction  is  merely  an  extension  of  the  Lederer-Manasse 
synthesis  discussed  on  p.  97  : 

N02  N02  N02  N02 

/\  H.CHO 


When  preparing  a  symmetrically  constituted  body 
the  synthesis  is  carried  out  in  one  step,  but  unsym- 
metrical  compounds  can  be  obtained  by  condensing 
benzyl  alcohol  or  nitrobenzyl  alcohol  with  nitrobenzene, 
benzene,  &c. 

PREPARATION  OF  3.3'-DINITRODIPHENYL  METHANE 
(C6H4NO2)2CH2.1  Twenty-four  grammes  of  nitrobenzene, 
120  grm.  of  concentrated  sulphuric  acid,  and  9  c.c.  of  40  per 
cent,  formaldehyde  are  heated  for  eight  days  to  4O°-5O°. 
Excess  of  nitrobenzene  is  then  removed  by  distillation  in 
steam,  and  the  solid  residue  collected,  washed,  and  recrystallised 
from  glacial  acetic  acid.  M.P.  174°. 

1  B.  27,  2322  ;   D.R.P.  67,001. 


CHAPTER  X 
THE  AMINO-COMPOUNDS 

THE  amino-compounds  may  be  divided  into  two 
groups,  viz.  the  AMINES,  R3C.NR2,  and  the  AMIDES, 
RCO.NR2,  where  R  may  be  hydrogen,  alkyl,  aryl,  or 
halogen.  Further,  the  amines  may  be  divided  into 
four  groups,  viz.  primary  amines,  RNH2,  secondary 
amines,  NR2H,  tertiary  amines,  NR3,  and  quater- 
nary ammonium  bases  or  their  salts,  NR4OH,  these 
last  containing  pentavalent  nitrogen.  The  amides 
form  secondary  and  tertiary  compounds,  but  not 
ammonium  bases.  For  convenience,  the  amino-com- 
pounds will  be  discussed  in  the  following  as  primary 
compounds,  secondary  compounds,  &c. 

THE  PRIMARY  COMPOUNDS 

i.  BY  THE  REDUCTION  OF  THE  NITRO- 
COMPOUNDS 

This  is  by  far  the  most  important  method  of  obtaining 
aromatic  primary  amines.  It  does  not  serve  for  the 
preparation  of  amides,  and  is  of  no  practical  importance 
in  the  aliphatic  series.  A  large  number  of  reducing 
agents  may  be  employed,  of  which  the  following  are 
the  most  important : 

METAL  AND  ACID.  The  metal  is  usually  zinc  (dust 
or  granulated),  tin,  or  iron,  and  the  acid,  dilute  sul- 
phuric, hydrochloric,  or  acetic,  but  hydrochloric  acid 
is  most  used.  In  the  case  of  tin,1  the  stannous  salt 

1  Pure  tin  is  only  attacked  slowly  by  hydrochloric  acid. 
This  can  be  remedied  by  adding  a  crystal  of  copper  sulphate. 

208 


THE  AMINO-COMPOUNDS  209 

is  first  formed,  but  this  is  further  acted  on,  stannic 
chloride  being  the  final  product  : 

Sn  +  2HC1  =  SnCl2  +  H2. 
SnCl2  +  2HC1  =  SnCl4  +  H2. 

Instead  of  tin  and  hydrochloric  acid  a  solution  of 
stannous  chloride  in  hydrochloric  acid  or  in  caustic 
alkali  (stannite)  is  often  used,  the  former  being  employed 
in  the  quantitative  estimation  of  nitro-groups.1  Tin 
reducing  agents  have  the  disadvantage  that  the  amino- 
compound  often  forms  a  tin  chloride  double  salt  which 
requires  further  treatment  before  the  free  base  can  be 
obtained.  Iron  and  hydrochloric  acid  is  the  reducing 
agent  used  on  the  large  scale,  and  also  gives  excellent 
results  in  the  laboratory.  The  iron  should  be  used 
as  powder,  or  as  filings  which  have  been  sifted  to  re- 
move the  larger  pieces.  Theoretically  only  a  very  small 
quantity  of  hydrochloric  acid  is  required  as  its  action 
is  catalytic,  e.g.  : 


+  48HC1  +  8C6H5NO2  =  24FeCl2  +  8C6H5NH2  +  i6H2O. 
24FeCl2  +  4C6H5N02  +  4H2O  -  i2Fe2Cl4O  +  4C6H5NH2. 
i2Fe2C!4O  +  9Fe  =  3Fe3O4 


9Fe  +  4H20  +  4C6H5N02  -  4C6H5NH2  +  3Fe3O4. 

On  the  large  scale  about  one-fortieth  of  that  required 
by  the  first  equation  is  used,  but  in  the  laboratory 
it  is  best  to  employ  about  one-twentieth,  unless  it 
is  desired  to  have  all  the  iron  in  solution  at  the  end, 
in  which  case  an  excess  of  acid  must  be  used. 

PREPARATION  OF  ANILINE  (C6H5NH2).  (a)  Fifty 
grammes  of  nitrobenzene  and  90  grm.  of  granulated  tin  are 
heated  on  a  water-bath  in  a  large  flask  provided  with  an  inverted 
air-condenser,  and  200  c.c.  of  technical  concentrated  hydro- 
chloric acid  added  slowly,  with  continual  shaking.  Much  heat 
is  evolved  and  the  liquid  boils.  If  the  reaction  becomes  too 

1  This  method  is  being  superseded  by  Knecht's  titanous 
chloride  method- 


210      PREPARATION  OF  ORGANIC  COMPOUNDS 

violent  it  should  be  moderated  by  cooling  the  flask  with 
water.  When  all  the  acid  has  been  added  (about  half  an  hour) 
the  whole  is  heated  on  the  water-bath  until  the  smell  of  nitro- 
benzene is  no  longer  noticeable.  The  contents  of  the  flask 
are  then  allowed  to  cool  until  the  stannic  chloride  double  salt 
begins  to  crystallise.  Concentrated  caustic  soda  solution  is 
then  slowly  added  until  almost  all  the  stannic  oxide  which  is 
first  precipitated  is  redissolved.  The  liquid  is  then  steam- 
distilled  until  the  distillate  comes  over  clear.  The  lower  layer 
of  the  distillate  is  drawn  off,  and  the  upper  aqueous  layer, 
which  contains  about  3  per  cent,  of  aniline,  saturated  with 
common  salt. /On  standing,  the  aniline  rises  to  the  surface, 
and  is  separated  from  the  brine  and  added  to  the  first  portion  of 
oil.  The  whole  is  then  distilled.  A  little  water  which  passes 
over  first  is  rejected,  the  aniline  itself  passing  over  at  182°. 
Instead  of  saturating  with  salt  as  above  the  aniline  may  be 
extracted  with  carbon  tetrachloride,  chloroform,  or  ether,  in 
which  case  the  solution  is  dried  with  anhydrous  potassium 
carbonate  and  the  solvent  removed  on  the  water-bath  before 
adding  the  main  portion  of  the  oil.  Almost  colourless 
liquid  which  soon  becomes  red.  Yield  about  90  per 
cent. 

(b)  Sixty  grammes  of  iron  powder  are  shaken  with  80  c.c. 
of  hot  water  and  a  few  drops  of  nitrobenzene.  Five  cubic 
centimetres  of  concentrated  hydrochloric  acid  are  added 
and  then,  little  by  little,  50  grm.  of  nitrobenzene.  After  each 
addition  of  nitrobenzene  the  flask  is  well  shaken  and  cooled 
with  water  so  that  the  temperature  keeps  between  80°  and 
90°.  When  all  the  nitrobenzene  has  been  added  and  no  more 
heat  is  evolved,  the  whole  is  steam-distilled  and  the  aniline 
collected  as  above.  Owing  to  the  small  quantity  of  acid 
used  there  is  no  need  to  make  the  contents  of  the  flask  alkaline 
before  steam-distilling  off  the  aniline.  Yield  about  90  per 
cent. 

PREPARATION  OF  £.-PHENYLENEDIAMINE  HYDRO- 
CHLORIDE  (NH2)2C6H42HC1.  Seventy  grammes  of  £.-nitro- 
acetanilide  and  150  grm.  of  sifted  iron  filings  are  mixed  with 
sufficient  water  in  a  large  flask  to  form  a  thin  cream.  Twenty 
cubic  centimetres  of  technical  hydrochloric  acid  are  then 
added,  and  the  whole  heated  on  the  water-bath  until  the 
reaction  sets  in  (about  90°) .  The  flask  is  then  at  once  removed 
from  the  water-bath  and  continually  shaken  until  its  contents 


THE  AMINO-COMPOUNDS  211 

no  longer  boil.  They  are  then  filtered  while  still  hot  into  a 
litre  of  concentrated  hydrochloric  acid  and  the  iron  residue 
washed  once  or  twice  with  a  little  boiling  water.  The  p.- 
phenylenediamine  hydrochloride,  which  is  insoluble  in  con- 
centrated hydrochloric  acid,  separates  out  from  the  filtrate, 
and,  after  cooling,  is  collected,  washed  with  concentrated  hydro- 
chloric acid,  and  dried  in  the  oven.  It  usually  has  a  pink 
colour,  due  to  the  oxidation  of  the  free  base  during  filtration. 
This  can  be  avoided  by  first  adding  a  few  cubic  centimetres 
of  sodium  bisulphite  solution.  The  yield  is  about  75  per  cent. 

PREPARATION  OF  a-NAPHTHYLAMINE  (C10H7NH2). 
Equal  weights  (about  50  grm.)  of  o-nitronaphthalene,  iron 
powder,  and  water  are  mixed  together  and  warmed,  and  a 
little  concentrated  hydrochloric  acid  (about  5  c.c.)  added. 
The  flask  must  be  well  shaken  and  the  temperature  kept  at 
about  80°.  When  no  more  heat  is  evolved  the  mixture  is 
made  alkaline  with  milk  of  lime,  cooled,  and  filtered.  The 
iron  residue  is  dried  in  the  air,  and  the  naphthylamine  either 
extracted  with  ether,  or  the  residue  is  carefully  distilled  in 
vacua  and  the  crude  naphthylamine  which  passes  over  redis- 
tilled under  reduced  pressure.  Yield  50  to  60  per  cent.  It 
may  be  recrystallised  from  dilute  alcohol,  and  melts  at  50°. 
Care  should  be  taken  to  prevent  its  coming  in  contact  with 
the  fingers  or  clothing  as  it  has  a  disgusting,  though  not  very 
strong,  odour. 

ALKALI  SULPHIDES.  The  alkali  sulphides  used  are 
the  sulphide,  M2S,  the  sulphhydrate,  MSH  (obtained 
by  saturating  a  solution  of  the  sulphide  with  H2S, 
and  then  removing  excess  of  the  latter  by  blowing  a 
current  of  hydrogen  through  the  liquid),  and  the  disul- 
phide,  M2S2  (obtained  by  boiling  an  aqueous  solution 
of  the  sulphide  with  one  equivalent  of  sulphur,  e.g. 
240  grm.  of  the  crystallised  sulphide,  200  c.c.  of  water, 
and  32  grm.  of  sulphur  are  boiled  under  a  reflux 
condenser  until  complete  solution  takes  place,  and  the 
solution  then  diluted  to  half  a  litre). 

The  sulphides  are  especially  useful  for  the  reduction 
of  nitrophenols,  but  reduction  only  takes  place  when 
the  nitro-group  is  not  in  the  ortho-  position  to  a  halogen 
atom,  another  nitro-group,  or  other  negative  radical. 


212      PREPARATION  OF  ORGANIC  COMPOUNDS 

When  such  or^o-substituents  are  present  one  of  the 
groups  is  split  out  and  replaced  by  — S.Ar  or  — SH 
(cf.  pp.  106,  152). 

The  following  equations  may  be  used  in  calculating 
the  amount  of  reducing  agent  required,  but  it  is  usually 
advisable  to  employ  an  excess  : 

R.NO2  +  Na2S  +  H2O  =  RNH2  +  Na2S(V 

4RN02  -f  6NaSH  +  H2O  =  4RNH2  +  3Na2S2O3. 

RNO2  +  Na2S2  +  H2O  =  RNH2  +  Na2S2O3. 

The  sulphides  are  also  useful  for  reducing  polynitro- 
compounds,  as  with  their  aid  it  is  often  possible  to  reduce 
one  nitro-group  without  affecting  the  others. 

PREPARATION  OF  m.-NITRANILINE  (C6H5NO2NH2).2 
(a)  Twenty  grammes  of  w.-dinitrobenzene  are  dissolved  in 
60  c.c.  of  alcohol,  and  16  grm.  of  concentrated  aqueous  ammonia 
added.  Sulphuretted  hydrogen  gas  is  then  passed  into  the 
solution,  which  should  be  warmed  from  time  to  time,  until  an 
increase  in  weight  of  12  grm.  has  taken  place.  The  nitraniline 
is  then  precipitated  with  water,  and  filtered  off  together  with  the 
sulphur  which  separates  during  the  reaction.  The  precipitate  is 
washed  with  a  little  cold  water,  and  then  extracted  several 
times  with  concentrated  hydrochloric  acid.  The  acid  extracts 
are  concentrated  somewhat,  cooled,  and  then  made  alkaline 
with  strong  ammonia.  The  precipitated  nitraniline  is  col- 
lected, washed  with  cold  water,  and  then  recrystallised 
from  boiling  water.  It  forms  yellow  needles  melting  at 

114°. 

(6)  Seventeen  grammes  of  w.-dinitrobenzene  are  dissolved 
in  170  c.c.  alcohol  and  the  whole  heated  to  boiling  under  a 
reflux  condenser.  A  concentrated  aqueous  solution  of  sodium 
sulphhydrate,  obtained  from  36  grm.  of  crystallised  sodium 
sulphide  (see  p.  211),  is  then  slowly  added.  The  alcohol  is 
then  distilled  off,  the  residue  diluted  somewhat  with  cold 
water,  filtered,  and  the  precipitate  recrystallised  from  boiling 
water. 

1  This    equation  is  very  unreliable  as  the  reaction  often 
takes  place  according  to  the  following  : 

ArN02  +  3H2S  =  ArNH2  +  38. 

2  A.  176,  44. 


THE  AMINO-COMPOUNDS  213 

HYDROSULPHITE.     Sodium  hydrosulphite,  Na2S2O4, 
is  one  of  the  best  reducing  agents  known  : 

H2O  +  Na2S2O4  +  O  =  2NaHSO3. 

The  reagent  can  be  applied  in  several  forms,  viz.  : 
(a)  As  the  dry,  powdered  sodium  salt,  usually  in  the 
presence  of  caustic  alkali.  The  most  satisfactory  form 
of  the  salt  is  the  concentrated  powder  put  on  the  market 
by  the  Badische  Company,  (b)  As  the  formaldehyde 
condensation  product,  known  commercially  as  "  sulph- 
oxylate."  (c)  In  the  nascent  state,  as  sodium 
bisulphite  and  sodium  formate  or  hypophosphorous 
acid,  or  as  zinc  dust  and  sodium  bisulphite.  Nitro- 
benzene itself  is  not  readily  attacked  by  hydro- 
sulphite,  but  nitrophenols  are  instantly  reduced. 

PREPARATION     OF    o.-    AND    p.- AMINOPHENOLS 

(C6H4(NH2)OH).  The  nitrophenol  is  dissolved  in  rather 
more  than  one  equivalent  of  dilute  caustic  soda  (about  10  per 
cent.}  and  the  solution  heated  to  boiling.  Dry  sodium 
hydrosulphite  powder  is  then  added  little  by  little  until  the 
red  colour  of  the  solution  disappears.  On  cooling,  the  ammo- 
phenol  separates  out  as  a  mass  of  colourless  crystals,  which 
are  filtered  off  and  washed  with  cold  water.  The  ortho- 
compound  melts  at  170°,  the  para-  at  184°. 

PREPARATION  OF  2.4  -  DIAMINO  -  i  -  NAPHTHOL  -  7  - 
SULPHONIC  ACID  HYDROCHLORIDE.1  Sixty  grammes  of 
sifted  zinc  dust  are  added  to  500  c.c.  of  technical,  40  per  cent. 
bisulphite  solution,  and  the  whole  shaken  until  a  rise  of 
temperature  is  felt.  Naphthol  Yellow  S  is  then  added  little  by 
little  to  the  mixture,  the  whole  being  well  shaken  after  each 
addition.  The  rate  of  addition  of  the  dyestuff  should  be 
regulated  so  that  the  liquid  is  kept  boiling  by  the  heat  of  the 
reaction.  When  a  permanent  red  coloration  is  obtained 
(about  80  grm.  of  Naphthol  Yellow  S  will  be  required)  the 
addition  of  the  dye  is  interrupted,  and  a  mixture  of  zinc  dust 
and  bisulphite  solution,  which  has  been  allowed  to  get  warm, 
is  added  until  the  colour  disappears.  The  solution  is  filtered 
while  still  hot  into  1500  c.c.  of  technical  concentrated  hydro- 

1  B. 14, 2029;  32,  232. 


2i4      PREPARATION  OF  ORGANIC  COMPOUNDS 

chloric  acid,  and  the  residue  washed  with  boiling  water.  The 
strongly  acid  liquors  are  allowed  to  stand  over -night,  and  then 
the  colourless  or  pink  amino-compound  filtered  off.  Yield 
67  per  cent. 

OK  OH 


NHo.HCl 


SO.H? 


NO2  NH2 

Naphthol  Yellow  S 

2.  BY  THE  REDUCTION  OF  THE  AZO- 
COMPOUNDS 

The  azo-compounds  are  very  readily  obtained  by 
the  action  of  the  diazo-salts  on  the  phenols  in  alkaline 
solution,  or  on  the  amines  in  acetic  acid  solution. 
The  azo-group  enters  the  para-  position  to  the  hydroxyl 
or  amino-group  if  this  position  is  unoccupied,  or  the 
ortho-  position  if  the  para-  is  not  available.  A  further 
discussion  will  be  found  on  p.  247. 

The  azo-compounds  on  reduction  undergo  rupture  at 
the  double  bond,  two  primary  amines  being  produced  : 

R.N  :N.R'  +  2H2  =  RNH2  +  R'NH2. 

This  method  of  preparing  amines  often  proves 
exceedingly  useful.  This  may  be  illustrated  by  the 
commercial  synthesis  of  phenacetin  (acetyl  />.-pheneti- 
dine),  which  is  carried  out  as  follows.  One  molecule 
of  ^.-phenetidine  is  diazotised  and  coupled  with  one 
molecule  of  phenol : 

EtO[i]C6H4[4]N 

EtO[i]C6H4[4]NH2  -*  || 

EtO[i]C6H4[4]N 

The  hydroxyl  group  of  the  resulting  azo-colour  is  then 
ethylated,  and  £.2-diethoxyazobenzene  reduced,  thus 
yielding  two  molecules  of  ^.-phenetidine  : 

EtO[i]C6H4[4]N  :N[4']C6H4[i']  +  2H2  = 

2EtO[i]C6H4[4]NH2. 
The  process  is  then  repeated  until  sufficient  />.-pheneti- 


THE  AMINO-COMPOUNDS  215 

dine  has  been  prepared,  which  is  then  converted  into 
phenacetin  by  acetylation. 

As  reducing  agents  for  azo-compounds  may  be  men- 
tioned, metal  and  acid,  stannous  chloride,  zinc  dust 
and  water  or  ammonia,  or  hydrosulphite  in  alkaline 
solution.  The  last  is  the  most  satisfactory.  The  re- 
action is  carried  out  by  dissolving  or  suspending  the 
azo-colour  in  water  containing  a  little  caustic  soda, 
and  then  adding  hydrosulphite  powder  to  the  boiling 
liquid  until  the  colour  is  discharged. 

PREPARATION   OF    £.-NAPHTHYLENEDI AMINE 

(C10H6[i.4](NH2)2).i  Aniline  (18-6  grm.)  is  dissolved  in 
500  c.c.  of  water  and  65  c.c.  of  technical  hydrochloric  acid. 
Ice  is  then  added  until  the  temperature  falls  below  o°,  and  the 
whole  diazotised  in  the  usual  way  with  a  solution  of  14.5  grm. 
of  sodium  nitrite  (see  p.  238).  a-Naphthylamine  (28-4  grm.)  is 
dissolved  in  cold  dilute  hydrochloric  acid  (about  400  c.c.  water 
and  100  c.c.  2N  acid) ,  and  the  solution  cooled  by  the  addition  of 
ice.  The  diazo-benzene  chloride  solution  prepared  as  above  is 
then  added  and  the  whole  mechanically  stirred.  Crystallised 
sodium  acetate  is  then  added  until  no  more  free  hydrochloric 
acid  is  present  (test  with  Congo  paper) .  The  separation  of  the 
azo-colour  commences  almost  at  once  and  is  complete  in  about 
two  hours,  during  which  time  the  solution  must  be  well  stirred 
and  the  temperature  kept  below  5°  by  the  addition  of  ice.  The 
precipitate  is  filtered  off,  well  washed  with  water,  and  dried  in 
the  steam-oven.  i-Aminonaphthylene-4-azo-benzene  forms 
red  needles  with  a  green  reflex.  The  yield  is  quantitative.  To 
reduce  it  to  the  diamine,  it  is  suspended  in  500  c.c.  of  water  and 
sifted  zinc  dust  slowly  added  to  the  boiling  suspension  until 
the  colour  is  discharged.  The  whole  is  then  filtered  hot  into 
500  c.c.  of  50  per  cent,  sulphuric  acid.  On  cooling,  the^.-naph- 
thylenediamine  separates  out  as  colourless  needles,  the  aniline 
remaining  in  solution  as  the  sulphate. 

NH2  NH2 

/\/\ 

+  C6H£NH2 


N  =  N.C6H5  NH2 

i  -Aminonaphthylene-4-azo-benzene      £.-Naphthylenediamine 

1   B.  22,  1381. 


216      PREPARATION  OF  ORGANIC  COMPOUNDS 


PREPARATION  OF  I.4-AMINONAPHTHOL  (C10H6[i] 
OH[4]NH2).1  One  hundred  grammes  of  technical  Orange  I 
are  dissolved  in  500  c.c.  of  boiling  water,  and  the  solution 
thus  obtained  poured  into  a  warm  solution  of  120  grin. 
of  stannous  chloride  in  half  a  litre  of  pure,  concentrated 
hydrochloric  acid.  Decolorisation  takes  place  almost  at  once 
(if  not,  more  stannous  chloride  must  be  added),  and  then  another 
200  c.c.  of  cold,  concentrated  acid  are  added,  and  the  whole 
well  stirred.  The  aminonaphthol  separates  as  the  hydro- 
chloride,  and  is  filtered  off  when  the  temperature  has  fallen 
to  about  45°.  It  is  washed  with  dilute  hydrochloric  acid. 
The  yield  is  about  36  grm. 


ONa 


OH 


NH9 


2H2  = 


Orange  I 


NH2 

i  .4- Amino- 
naphthol 


S03H 

Sulphanilic 
acid 


PREPARATION      OF      a-AMINO-/3-NAPHTHOL.2     A 

warm  solution  of  130  grm.  of  tin  in  750  c.c.  of  technical  hydro- 
chloric acid  is  added  to  100  grm.  of  Orange  II  (Mandarin) 
in  i  litre  of  boiling  water.  After  decolorisation  has  taken 
place  the  solution  is  filtered  as  rapidly  as  possible.  On 
cooling,  the  aminonaphthol  separates  from  the  filtrate  as  the 
hydrochloride  (colourless  crystals). 

NH, 


OH 


Orange  II  (Mandarin) 


a-Amino- 
/3-naphthol 


S03H 


Sulphanilic 
acid 


Both  the  above  aminonaphthols  can  also  be  prepared 
by   treating  boiling   alkaline   solutions   of   Orange   I 


B.  25,  423- 


2  B.  25,  980. 


THE  AMINO-COMPOUNDS 


217 


or  II  with  hydrosulphite  until  decolorisation  takes 
place.  On  cooling,  the  aminonaphthol  separates 
out. 

3.   THE   BENZIDINE   AND   SEMIDINE  CHANGE 

Aromatic  hydrazo-compounds  when  treated  with 
acids  undergo  an  intramolecular  rearrangement  whereby 
a  diphenyl  derivative  is  formed,  e.g. : 


C6H5.NH.NH.C6 

Hydrazobenzene 


NH2.C6H4.C6H4.NH 

Benzidine 


When  both  para-  positions  are  unoccupied,  as  in  the 
above  example,  a  ^>.2-diaminodiphenyl  is  formed  ("  para- 
benzidine  change").  When  one  or  both  of  the  para- 
positions  are  occupied,  either  an  o.2-diaminodiphenyl 
("  or^o-benzidine  change ")  or  an  ortho-  or  para- 
semidine  is  formed,  e.g.  : 


CH3 

/\ 


NH 


NH 


/' 


\/ 

CH3 


CH, 


NH 


NH, 


CH, 


An  o^/zo-semidine 

For  a  discussion  on  the  benzidine  and  semidine 
change  the  reader  is  referred  to  Stewart's  "  Stereo- 
chemistry," p.  396. 

The  change  is  brought  about  by  the  action  of  acids. 

PREPARATION  OF  BENZIDINE  (NH2[4]C6H4.C6H4 
[4/]NH2).  (a)  From  hydrazobenzenel  Five  grammes  of 

1  J-  pr.  [i]  36,  93- 


2i8      PREPARATION  OF  ORGANIC  COMPOUNDS 

powdered  hydrazobenzene  are  shaken  with  125  c.c.  of  3  per 
cent,  hydrochloric  acid  at  a  temperature  of  2O°-3O°  until 
dissolved.  The  solution  is  then  warmed  to  50°,  and  any 
benzidine  hydrochloride  which  separates  redissolved  by  the 
addition  of  water.  The  solution  is  filtered  while  still  warm. 
Excess  of  cold  caustic  soda  is  added  to  the  nitrate,  and  the 
precipitated  benzidine  collected,  washed  with  cold  water,  and 
recrystallised  from  boiling  water  or  dilute  alcohol.  Colourless 
plates  melting  at  127°. 

(b)  From  azobenzene*  Ten  grammes  of  azobenzene  are 
dissolved  in  alcohol,  and  the  solution  warmed  with  a  solution  of 
3-5  grm.  of  tin  in  10  c.c.  concentrated  hydrochloric  acid. 
When  decolorisation  has  taken  place  the  alcohol  is  removed 
by  distillation,  the  residue  dissolved  in  water,  and  the  benzidine 
precipitated  as  the  insoluble  sulphate  by  dilute  sulphuric  acid. 
The  precipitate  is  washed  free  from  tin,  first  with  dilute  hydro- 
chloric acid  and  then  with  water,  and  finally  decomposed  with 
ammonia.  The  free  base  thus  obtained  is  filtered  off  and 
recrystallised  as  above. 

Some  aniline  is  also  formed  in  the  above  reaction  (see 
p.  214). 

4.  BY  THE  REPLACEMENT  OF  HALOGEN 
ATOMS 

Halogen  atoms  can  be  replaced  by  the  amino- 
group  by  heating  the  halogen  compound  with  ammonia 
or  ammonium  carbonate,  or  with  potassium  phthali- 
mide,  and  then  hydrolysing  the  resulting  phthalimide 
derivative  (Gabriel's  method)  : 


)N.K  +  R.C1 


—CO- 


\ 


NR  +  KC1 


— CO- 


j— CO,  /N—COOH 

>NR  +  2H20    =  +  RNH2 

I— OX  I        I— COOH 

The  method  is  of  very  little  value  with  aromatic 
halogen   compounds   unless   nitro-  or  other  negative 

1  Schultz,  "  Chemie  des  Steinkohlenteers  "  [1886],  s.  359. 


THE  AMINO-COMPOUNDS  219 

groups  are  present  in  the  ortho-  or  para-  position  to 
the  halogen  atom,  but  it  is  very  useful  for  preparing 
aliphatic  amines,  and  Gabriel's  modification  of  the 
method  has  proved  of  considerable  value  in  the  study 
of  the  amino-acids. 

For  preparing  acid  amides,  the  action  of  the  acid 
chloride  on  ammonia  is  the  most  frequently  used  method, 
the  reaction  in  nearly  all  cases  taking  place  readily  at  the 
ordinary  temperature.  For  this  purpose  it  is  not 
necessary  to  isolate  the  chloride  in  the  pure  state,  but 
merely  to  use  the  impure  product  prepared  as  described 
on  p.  68. 

PREPARATION  OF  GLYCOCOLL  (GLYCINE)  (NH2.CH2. 
COOH)  (a)  One  hundred  grammes  of  chloracetic  acid  are 
dissolved  in  an  equal  weight  of  water,  and  the  solution  thus 
obtained  slowly  run  into  1200  c.c.  of  25  per  cent,  ammonia, 
the  whole  being  well  stirred.  After  all  the  acid  has  been 
added  the  solution  is  allowed  to  stand  for  twenty-four  hours, 
and  then  boiled  in  a  basin  until  it  no  longer  smells  of  ammonia. 
(It  is  important  to  get  rid  of  all  the  ammonia.)  It  is  then 
neutralised  while  hot  with  a  slight  excess  of  copper  carbonate, 
filtered,  and  the  filtrate  evaporated  until  crystallisation  sets  in. 
On  cooling,  the  copper  salt  of  glycocoll  separates  out  (blue 
needles)  and  is  filtered  off  and  washed,  first  with  dilute,  and 
then  with  stronger  alcohol.  It  is  dissolved  in  water,  and  the 
copper  precipitated  from  the  boiling  solution  by  hydrogen  sul- 
phide. The  copper  sulphide  is  filtered  off  and  well  washed,  and 
the  filtrate  concentrated  to  a  small  bulk.  On  cooling,  the 
glycocoll  separates  out  as  monoclinic  crystals  which  melt  with 
decomposition  rather  indefinitely  at  2^2°-2^6°.  It  is  soluble 
in  4  parts  of  cold  water,  but  almost  insoluble  in  alcohol  and 
ether. 

(b)  *  One  hundred  grammes  of  potassium  phthalimide  and 
65  grm.  of  chloracetic  ester  are  heated  for  an  hour  and  a  half  to 
140°-!  50°,  and  the  resulting  liquid,  while  still  hot,  poured  into  a 
basin.  After  cooling,  the  solid  mass  is  ground  up  and  dissolved 
in  50  per  cent,  boiling  alcohol.  On  cooling,  the  phthalimide 

/C°\ 
compound,  C6H4<^         ^N.CH2CO2Et,  separates   out   and   is 

>CCK 

1    B.    22,    426. 


220      PREPARATION  OF  ORGANIC  COMPOUNDS 

washed  free  from  potassium  chloride  with  dilute  alcohol.  The 
yield  is  95  per  cent.  The  hydrolysis  is  best  effected  in  two 
steps.  One  molecule  of  the  above  compound  is  boiled  for  a 
short  time  with  two  molecules  of  10  per  cent,  caustic  potash, 
and  the  solution  then  allowed  to  cool  completely.  Two 
molecules  of  concentrated  hydrochloric  acid  are  then  added, 
the  whole  cooled  to  o°,  and  the  o.-carboxylbenzoyl  glycocoll, 
COOH[i]C6H4[2]CONH.CH2COOH,  which  separates  out  fil- 
tered off,  and  washed  with  ice-water  until  free  from  chloride. 
It  forms  colourless  leaflets  which  sinter  at  100°,  and  melt  at 
iO5°-io6°.  The  yield  is  85  per  cent.  To  bring  about  the 
second  stage  of  the  hydrolysis,  the  above  compound  is  refluxed 
for  two  hours  with  twice  its  weight  of  20  per  cent,  hydrochloric 
acid,  the  flask  being  well  shaken  from  time  to  time.  A  clear 
solution  is  at  first  obtained,  but  phthalic  acid  soon  begins  to 
separate.  After  cooling,  the  liquid  is  filtered,  and  evaporated 
on  the  water-bath  to  dryness.  The  residue  is  extracted  with 
not  too  much  ice-cold  water,  filtered  from  the  undissolved 
phthalic  acid,  and  the  filtrate  concentrated.  The  glycocoll 
which  separates  on  cooling  is  washed  with  ice-cold  alcohol. 

PREPARATION  OF  OLEAMIDE  (CH3(CH2)?CH  ;  CH. 
(CH2)7.CONH2).1  Twenty  grammes  of  pure  oleic  acid  are 
well  mixed  with  4  grm.  of  phosphorus  trichloride,  and  the 
whole  after  standing  for  a  short  time  gently  warmed.  The 
solution  thus  obtained  is  slowly  dropped  into  300  c.c.  of  con- 
centrated ammonia.  The  precipitate  is  filtered  off,  ground  up 
with  2  per  cent,  caustic  soda  solution,  well  washed  with  water, 
and  then  recrystallised  from  dilute  alcohol.  Colourless 
scales  melting  at  75°-76°.  Yield  80  per  cent. 

Other  acid  amides  can  be  obtained  in  exactly  the 
same  way,  but  the  amides  of  the  lower  fatty  acids 
are  soluble  in  water,  and  as  they  are  also  steam-volatile 
they  must  be  isolated  by  evaporating  the  ammo- 
niacal  liquors  at  the  ordinary  temperature. 

5.  BY  THE  REPLACEMENT  OF  HYDROXYL  GROUPS 

When  phenol  is  heated  with  ammonia  under  pressure 
but  little  aniline  is  formed.  Amino-compounds, 
however,  are  readily  formed  when  polyhydric  phenols 

1  B.  31,  2349. 


THE  AMINO-COMPOUNDS  221 

or  naphthols  are  heated  with  ammonia,  and  this  method 
is  used  on  the  large  scale.  The  ammonia  is  applied 
either  as  a  concentrated  aqueous  solution,  or  as  its 
addition  compound  with  zinc  or  calcium  chloride, 
MC12 .  2NH3.  The  zinc  chloride  compound,  ZnCl22NH3, 
is  obtained  by  passing  dry  ammonia  over  powdered 
anhydrous  zinc  chloride  as  long  as  any  gas  is  absorbed  ; 
or  ammonia  gas  can  be  passed  into  the  molten  chloride. 
In  either  case  the  reaction  takes  place  with  considerable 
evolution  of  heat,  and  a  hard  mass  is  obtained  which 
must  be  preserved  in  well-stoppered  bottles. 

PREPARATION  OF  w.- AMINOPHENOL  (C6H4[i]NH2 
[3JOH).1  Ten  grammes  of  resorcinol,  6  grm.  of  ammonium 
chloride,  and  20  grm.  of  10  per  cent,  ammonia  are  heated  in 
a  sealed  tube  to  200°  for  ten  hours.  After  cooling,  the  reaction 
mixture  is  made  strongly  acid  with  hydrochloric  acid  (a 
large  excess  of  acid  must  be  used)  and  then  unchanged  resor- 
cinol extracted  with  ether.  On  neutralising  the  residue  with 
caustic  soda,  part  of  the  aminophenol  separates  and  is  filtered 
off.  The  rest  is  extracted  with  ether  and  the  ether  removed 
by  distillation.  The  aminophenol  is  finally  purified  by  re- 
crystallisation  from  toluene.  It  melts  at  122°. 

PREPARATION  OF  /3-NAPHTHYLAMINE  (C10H7NH2).a 
Sixty  grammes  of  /3-naphthol  and  240  grm.  of  powdered 
zinc  ammonia  chloride  are  well  mixed  and  heated  on  an  oil- 
bath  under  a  reflux  condenser  for  two  hours  to  200°.  After 
cooling,  25  per  cent,  caustic  soda  solution  is  added  until  the 
zinc  oxide  at  first  precipitated  is  redissolved,  and  the  solution 
then  boiled  for  a  few  minutes.  After  cooling,  the  naphthyl- 
amine  is  extracted  with  ether,  the  ether  removed  by  distillation, 
and  the  naphthylamine  purified  by  recrystallisation  from 
water  or  dilute  alcohol.  It  forms  colourless  plates  melting  at 
112°.  Instead  of  extracting  with  ether,  the  base  can  be  isolated 
by  distillation  with  superheated  steam.  The  distillate  is 
concentrated  and  the  naphthylamine  which  separates  collected 
and  recrystallised. 

1  Am.  15,  40. 

2  B.  13,  1300.    Cf.  Cain  and  Thorpe,  "  Synthetic  Dyestuffs," 

p.  221. 


222      PREPARATION  OF  ORGANIC  COMPOUNDS 

The  sulphurous  esters  of  the  phenols  react  with 
ammonia  much  more  readily  than  the  phenols  them- 
selves, and  are  thus  well  adapted  for  the  preparation  of 
primary  amines.  In  carrying  out  the  reaction  the 
ester  is  not  isolated,  but  a  mixture  of  the  phenol, 
ammonium  sulphite,  and  ammonia  is  heated  under 
pressure.  This  method  gives  almost  quantitative 
yields  of  /3-naphthylamine  from  /3-naphthol.  For 
further  details  the  reader  is  referred  to  the  original 
literature.1 

Salts  of  organic  acids  as  a  rule  are  not  very  readily 
attacked  by  ammonia  (see  p.  266),  but  acid  amides 
can  often  be  obtained  by  the  action  of  concentrated 
ammonia  on  the  esters. 

PREPARATION  OF  OXAMIDE  (CONH2)2.  Five  grammes 
of  diethyl  oxalate  are  slowly  added  to  50  c.c.  of  concentrated 
ammonia  (D  =  0-88).  After  dilution  the  white  crystalline 
precipitate  is  filtered  off  and  well  washed.  On  heating,  it 
decomposes  with  partial  sublimation. 

A  standard  method  for  preparing  acid  amides  consists 
in  heating  the  ammonium  salts  of  the  acids. 

PREPARATION  OF  ACET AMIDE  (CH3CO.NH2).  Fifty 
grammes  of  ammonium  acetate  are  melted  and  poured  into  a 
bomb  tube  which  has  been  previously  warmed.  The  tube  is 
then  sealed,  and  heated  to  200°  for  six  hours.  The  resulting 
liquid  is  distilled  and  the  portion  boiling  above  180°  collected. 
This  on  standing  solidifies,  and  is  freed  from  mother-liquor  by 
pressing  between  filter-paper.  The  solid  mass  thus  obtained  is 
redistilled  (B.P.  222°),  and  the  distillate,  which  has  a  strong 
smell  of  mice,  recrystallised  from  benzene.  Colourless,  almost 
odourless  crystals  melting  at  82°  and  boiling  at  222°.  Yield 
about  50  per  cent. 

i  D.R.P.  117,471,  121,683;  J.  pr.  [2]  69,  49,  ;  70,  345; 
7J>  433  ;  75,  249  ;  77,  403  ;  79,  369  ;  80,  201. 


THE  AMINO-COMPOUNDS  223 

6.  BY  THE  DISRUPTION  OF  THE  ACID  AMIDES 
(HOFMANN'S  REACTION) 

This  reaction  provides  a  ready  means  of  preparing 
amino-compounds  from  acid  amides,  and  is  employed 
technically  for  the  preparation  of  anthranilic  acid 
from  phthalimide,  anthranilic  acid  being  an  inter- 
mediate compound  in  the  manufacture  of  indigo. 
The  reaction  is  brought  about  by  the  action  of  hypo- 
bromite  (on  the  large  scale  hypochlorite  is  used)  and 
caustic  soda,  and  probably  takes  place  in  the  following 
steps  : 

R.CONH2     55     R.CO.NHBr         NaOH         R— C— ONa 

Tautomeric  || 

change       Br — N 

H-l-  OH 
Br-l-C  —  ONa 

9.         i    11 

RNH2+Na2C03+NaBr     ^oH  Tl II 

H2      R.N 

The  third  step,  it  will  be  observed,  is  analogous  to 
the  Beckmann  rearrangement  of  the  oximes  (see  p.  232). 

PREPARATION  OF  METHYLAMINE  HYDROCHLORIDE 

(CH3NH2 .  HC1) .  Thirty  grammes  of  dry  acetamide  are  mixed 
with  80  grm.  of  bromine,  and  the  mixture  well  cooled  with  cold 
water.  A  10  per  cent,  solution  of  caustic  potash  is  then  added 
until  the  colour  of  the  liquid  passes  from  red  to  yellow.  The 
solution  thus  obtained  is  added  slowly  to  a  solution  of 
75  grm.  of  caustic  potash  in  150  c.c.  of  water.  Considerable 
heat  is  evolved,  and  care  must  be  taken  not  to  allow  the  tem- 
perature to  exceed  75°.  When  all  the  solution  has  been  added, 
the  whole  is  maintained  at  this  temperature  for  half  an  hour 
and  then  distilled,  and  the  distillate  absorbed  in  dilute 
hydrochloric  acid.  During  the  distillation  the  liquid  is 
apt  to  bump  violently,  but  this  can  be  remedied  to  a  large 
extent  by  adding  porous  pot,  or  by  blowing  a  fine  stream  of  air 
through  the  liquid  (see  p.  23).  When  the  distillate  no  longer 
comes  over  alkaline,  the  hydrochloric  acid  is  evaporated  to 


224      PREPARATION  OF  ORGANIC  COMPOUNDS 

dryness,  and  the  residual  mixture  of  methylamine  hydrochloride 
and  ammonium  chloride  repeatedly  extracted  with  small 
quantities  of  boiling  absolute  alcohol,  in  which  the  ammonium 
salt  is  insoluble.  On  cooling  the  alcoholic  extracts,  the 
methylamine  hydrochloride  separates  as  colourless,  deliquescent 
leaflets  which  melt  at  227°.  The  yield  is  about  85  per 
cent. 

PREPARATION  OF  ANTHRANILIC  ACID  (C6H4[i]NH2 
[2JCOOH).1  Fifty  grammes  of  finely  powdered  phthalimide 
and  100  grm.  of  caustic  soda  are  dissolved  simultaneously 
in  350  c.c.  of  water.  Half  a  litre  of  a  5  per  cent,  solution 
of  sodium  hypochlorite  is  then  slowly  run  in,  the  liquid  being 
well  shaken  during  the  operation.  When  all  the  hypochlorite 
has  been  added,  the  whole  is  warmed  for  a  few  minutes  to  80°, 
cooled,  and  accurately  neutralised  with  hydrochloric  acid.  An 
excess  of  strong  acetic  acid  is  then  added,  when  the  greater 
part  of  the  anthranilic  acid  separates  as  a  crystalline  precipi- 
tate, and  is  filtered  off,  and  washed  with  cold  water.  The 
liquors  are  treated  with  copper  acetate  solution  as  long 
as  any  precipitation  takes  place,  the  copper  anthranilate 
filtered  off,  washed,  and  then  decomposed  by  suspending  in  a 
little  boiling  water  and  passing  sulphuretted  hydrogen  through 
the  liquid.  The  precipitated  copper  sulphide  is  removed  by 
filtration,  and  the  filtrate  allowed  to  cool.  The  anthranilic 
acid  crystallises  out  and  is  filtered  off.  A  further  quantity 
may  be  obtained  by  evaporating  the  filtrate.  The  acid  is 
finally  purified  by  recrystallisation  from  water.  It  forms 
colourless  or  slightly  yellow  leaflets  which  melt  at  144°- 145°. 

7.  FROM  THE  NITRILES 

In  the  saponification  of  the  nitriles  the  acid  amide 
is  the  first  product.  When  the  saponification  is  brought 
about  by  boiling  with  alkalis  or  acids,  the  amide  cannot 
be  readily  isolated  as  it  undergoes  further  decomposition : 

R.C  =  N  ->  R.CO.NH2  ->  R.COOH+NH3. 
When,  however,  the  hydrolysis  is  brought  about  by 
hydrogen  peroxide  in  the  presence  of  dilute  caustic 
soda,  the  reaction  does  not  proceed  beyond  the  first 
stage,  and  the  amide  can  often  be  obtained  in  almost 
i  D.R.P.  55,988, 


THE  AMINO-COMPOUNDS  225 

theoretical  yield.  The  reaction  is  brought  about  by 
shaking  the  nitrile  with  10  or  20  volume  hydrogen 
peroxide  containing  some  caustic  soda.  The  reaction 
goes  best  at  a  temperature  of  about  40°. 

PREPARATION  OF  BENZ AMIDE  (CgH^ONH,,).1  Ten 
grammes  of  benzonitrile  are  added  to  150  c.c.  of  10  volume 
(3  per  cent.}  aqueous  hydrogen  peroxide  to  which  2  or  3  c.c. 
of  10  per  cent,  caustic  soda  solution  have  been  added.  The 
whole  is  warmed  to  40°,  and  then  violently  shaken  until 
the  oil  has  completely  given  place  to  a  white  precipitate. 
This  is  filtered  off,  and  recrystallised  from  alcohol.  M.P.  163°. 
During  the  shaking  an  opening  must  be  left  for  the  oxygen 
evolved  to  escape  : 

C6H5CN  +  H202  =  C6H5CO.NH2  +  O. 
The  yield  is  quantitative. 

Primary  amines,  R.CH2NH2,  can  also  be  obtained 
by  reducing  the  nitriles.2  The  reduction  is  carried  out 
with  zinc  and  sulphuric  or  hydrochloric  acid,  usually 
in  alcoholic  solution,  or  with  sodium  and  alcohol.  In 
the  latter  case  the  nitrile  is  dissolved  in  10-15  parts 
of  alcohol,  and  about  four  times  the  calculated  amount 
of  sodium  rapidly  added  to  the  boiling  solution.  Under 
these  conditions  aromatic  nuclei,  if  present,  are  simul- 
taneously reduced.  The  yields  are  usually  rather  poor, 
as  part  of  the  nitrile  is  hydrolysed  to  the  acid  and  part 
completely  reduced  : 

RCN  +  H2  =  RH  +  HCN. 

THE  SECONDARY  AND  TERTIARY  COMPOUNDS 
i.  FROM  THE  HALOGEN  COMPOUNDS 

Just  as  primary  amines  are  obtained  from  the  halogen 
compound  and  ammonia,  so  also  are  the  secondary  and 
tertiary  amines  obtained  respectively  from  the  primary 
and  secondary  bases  : 

RNH2  +  RC1  =  R2NH  +  HC1. 

R2NH  +  RC1  =  R3N  +  HC1. 

1  B.  18,355.      2  B.  18,2957;  19,  782;  20,  1709;  24,  3355. 


226      PREPARATION  OF  ORGANIC  COMPOUNDS 

When  an  aliphatic  halogen  compound  is  treated  with 
ammonia,  primary,  secondary,  tertiary,  and  quaternary 
compounds  are  all  formed  : 

RCl  RCl  RCl 

RC1  +  NH3  —  RNH2  ->  R2NH  -*  R3N  —  R4N.C1. 

In  the  aromatic  series  the  formation  of  secondary  and 
tertiary  bases  proceeds  much  less  readily,  and  to  obtain 
satisfactory  yields  it  is  necessary  to  employ  a  catalyst. 
It  has  been  found  that  the  presence  of  cuprous  chloride 
or  finely  divided  copper  greatly  accelerates  the  splitting 
out  of  halogen  acid  between  a  molecule  of  an  aliphatic 
or  aromatic  halogen  compound  and  a  primary  or  secon- 
dary base,  phenol  or  mercaptan.  It  is  only  necessary 
to  use  a  trace  of  copper  powder.  The  copper  powder 
can  be  made  by  sifting  zinc  dust  into  a  cold,  saturated 
solution  of  copper  sulphate,  as  described  on  p.  75. 
Copper  powder  can  also  be  bought  under  the  name  of 
"  copper  bronze  "  or  "  Naturkupfer  C."  These  contain 
a  trace  of  oil,  and  before  use  must  be  well  washed  with 
ether  or  petroleum  spirit. 

The  copper-powder  method  has  been  very  largely 
employed  in  the  aromatic  series,  and  the  following 
rules  are  fairly  general : 

Primary  aromatic  base  +  aliphatic  halogen  com- 
pound. Both  secondary  and  tertiary  bases  are  obtained 
with  ease. 

Primary  aromatic  base  +  aromatic  halogen  com- 
pound. The  secondary  base  only  is  formed,  but,  as 
a  rule,  tertiary  bases  can  be  obtained  by  using  the 
aromatic  iodide. 

Secondary  mixed  base  +  aromatic  halide.  The 
tertiary  base  is  formed,  although  it  is  often  necessary 
to  employ  the  bromide  or  iodide. 

In  carrying  out  the  reaction  it  is  usual  to  add  some 
substance,  such  as  anhydrous  sodium  acetate  or  sodium 
carbonate,  to  absorb  the  halogen  acid  liberated.  Any 
neutral  solvent,  such  as  nitrobenzene,  benzene, 
naphthalene,  amyl  alcohol,  &c.,  can  be  used,  or,  with 
liquid  or  easily  fusible  bases,  a,n  excess  of  the  base 


THE  AMINO-COMPOUNDS  227 

can  be  used  without  a  solvent.  If  it  is  desired  to 
prepare  a  secondary  base  it  is  best  to  use  a  large 
excess  of  the  primary  amine,  especially  if  condensation 
is  taking  place  with  an  aliphatic  halogen  compound. 
When  preparing  tertiary  bases  an  excess  of  the  halogen 
compound  is  used. 

PREPARATION  OF  PHENYLGLYCINE-o.-CARBOXYLIC 
ACID  (COOH[2]C6H4[i]NH.CH2COOH).i  Twenty  grammes 
of  potassium-o.-chlorbenzoate  or  an  equivalent  amount  of 
the  free  acid,  5-6  grm.  of  caustic  potash,  7  grm.  of  potassium 
carbonate,  7-5  grm.  of  glycocoll,  15  c.c.  of  water,  and  about 
o-i  grm.  of  copper  powder  are  heated  to  boiling  under  a  reflux 
condenser  on  the  oil-bath  for  one  hour.  The  liquid  becomes 
at  first  blue,  then  green,  and  finally  yellow.  Boiling  water 
is  then  added  until  the  crystals  which  have  separated  pass 
into  solution,  and  the  whole  filtered  into  excess  of  hydro- 
chloric acid.  The  phenylglycine-o.-carboxylic  acid  separates 
out  in  almost  quantitative  yield,  and  is  purified  by  recrystallisa- 
tion  from  water.  It  melts  with  decomposition  at  207°. 

PREPARATION   OF  N.-METHYL   ANTHRANILIC  ACID,2 

C6H4    iT      Anthranilic    acid    (13-7   grm.)    is    dissolved 


in  140  c.c.  of  water  and  accurately  neutralised  with  caustic 
potash.  Methyl  iodide  (14-5  grm.)  is  then  added,  and  the  whole 
boiled  under  a  reflux  condenser  for  several  hours  until  the 
methyl  iodide  has  disappeared.  After  cooling,  the  methyl 
anthranilic  acid  is  filtered  off,  washed,  and  recrystallised  from 
alcohol.  M.P.  179°. 

PREPARATION    OF    N.-PHENYL    ANTHRANILIC    ACID 

(C6H4[i]NHC6H5[2]COOH).  (a)3  Twenty  grammes  of  an- 
thranilic acid,  32  grm.  of  bromobenzene,  20  grm.  of  anhydrous 
sodium  carbonate,  and  about  i  grm.  of  Naturkupfer  C  are 
boiled  under  a  reflux  condenser  with  120  grm.  of  nitrobenzene 
for  three  hours.  The  nitrobenzene  is  then  removed  by 
distillation  with  steam,  and  the  aqueous  residue  filtered, 
cooled,  and  acidified  with  hydrochloric  acid.  The  greenish 
crystals  which  separate  are  washed,  dried,  and  then  recrystal- 
lised from  benzene.  M.P.  186°  (cor.).  Yield  95  per  cent. 

1  D.R.P.  142,507  ;    cf.  also  142,506. 

2  M.  21,  930.  3  B.  39,  1691. 


228      PREPARATION  OF  ORGANIC  COMPOUNDS 

(b)  *•  Twenty  grammes  potassium-o.-chlorbenzoate,  10  grm. 
of  aniline  and  0*2  grm.  of  copper  powder  are  boiled  for  thirty 
hours  with  100  c.c.  of  water.  After  cooling,  the  crystals 
which  separate  are  filtered  off,  washed  free  of  aniline  with 
dilute  hydrochloric  acid,  and  then  recrystallised  from  alcohol. 
Yield  80  per  cent. 

The  acyl  amino-compounds,  R.NH.CO.R,  are  ob- 
tained (a)  by  heating  the  primary  amine  with  the 
acid ;  (b)  by  heating  the  amine  with  the  acid  anhydride 
with  or  without  a  condensing  agent,  such  as  the  anhy- 
drous sodium  salt,  sulphuric  acid,  &c.  ;  (c)  by  treating 
the  amine  with  the  acid  chloride,  either  alone  or, 
in  the  case  of  stable  chlorides  such  as  benzoyl  chloride, 
in  the  presence  of  10  per  cent,  aqueous  caustic  soda 
(Schotten-Baumann  method),  sodium  carbonate,  lime, 
chalk,  &c.  For  a  full  description  of  these  and  other 
methods  the  reader  is  referred  to  Chapter  I  of  Lassar- 
Cohn's  "  Arbeit  smethoden." 

The  secondary  amines  are  only  acylated  with  diffi- 
culty, and  usually  require  prolonged  heating  with  the 
acid  anhydride  and  a  condensing  agent. 

With  aromatic  acid  chlorides  the  Schotten-Baumann 
method  usually  gives  excellent  results.  The  primary 
amine  is  suspended  in  10  per  cent,  aqueous  caustic 
soda,  and  an  excess  of  the  acid  chloride  added  little 
by  little,  the  solution  being  shaken  after  each  addition 
until  all  the  chloride  has  disappeared. 

Good  results  are  also  obtained  by  heating  the  amine 
with  the  acid,  acid  anhydride  or  acid  chloride,  in 
nitrobenzene  or  naphthalene  solution. 

PREPARATION  OF  ACETANILIDE  (C6H5NH .  COCH3) . 
(a)  Twenty  grammes  of  aniline  and  15  grm.  of  glacial  acetic 
acid  are  boiled  under  a  reflux  condenser  for  twelve  hours. 
The  condenser  should  be  simply  a  wide  glass  tube,  long  enough 
to  condense  the  acid  and  aniline,  but  not  the  water  evolved 
during  the  reaction.  The  product  is  poured  into  hot  water 
containing  a  little  hydrochloric  acid,  cooled,  filtered,  and 
the  precipitate  recrystallised  from  boiling  water  or  dilute 
alcohol,  Colourless  leaflets.  M.P.  115°. 

i  D.R.P.  145,189  ;   B.  36,  2382, 


THE  AMINO-COMPOUNDS  229 

(b)  Aniline  is  slowly  added  to   its  own  weight  of  acetic 
anhydride,  contained  in  a  flask  fitted  with  a  reflux  condenser. 
Much  heat  is  evolved,  and  after  all  the  aniline  has  been  added 
the  whole  is  gently  boiled  for  a  few  minutes.     It  is  worked  up 
exactly  as  above. 

(c)  Aniline  is  slowly  added  to  its  own  weight  of  acetyl 
chloride,  the  whole  warmed  on  the  water-bath  and  poured 
into  water. 

PREPARATION  OF  BENZANILIDE  (C6H5NH .  COC6H5) . 
Eight  grammes  of  aniline  are  shaken  up  with  about  150  c.c. 
of  cold  10  per  cent,  caustic  soda.  Fourteen  grammes  of 
benzoyl  chloride  are  added  in  four  portions,  and  after 
each  addition  the  solution  is  vigorously  shaken  until  the  smell 
of  benzoyl  chloride  disappears.  Care  must  be  taken  to  avoid 
.  rise  in  temperature.  When  all  the  benzoyl  chloride  has  been 
used,  the  benzanilide  is  filtered  off,  washed  with  cold  water, 
and  recrystallised  from  dilute  alcohol.  M.P.  165°. 

PREPARATION  OF  BENZOYL  -  a  -  AMINOANTHRA  - 
QUINONE  (C14H7O2NHCOC6H5).i  Ten  grammes  of  a-amino- 
anthraquinone,  100  grm.  of  nitrobenzene,  and  20  grm.  of  benzoyl 
chloride  are  boiled  under  a  reflux  condenser  for  half  an  hour. 
On  cooling,  the  benzoyl  compound  separates  out,  and  is  collected 
and  washed  with  alcohol  or  ether.  It  forms  a  yellow  crystalline 
powder  which  dyes  cotton  bright  yellow  from  an  alkaline 
hydrosulphite  vat.  It  is  the  Algol  yellow  W.G.  of  commerce. 

By  the  above  methods  acid  anilides  are  readily 
obtained  from  almost  all  primary  aromatic  amines, 
such  as  the  toluidines,  naphthylamines,  &c. 

PREPARATION  OF  HIPPURIC  ACID  (C6H5CO.NH. 
CH2.COOH).2  Fifteen  grammes  of  finely  powdered  glycocoll 
are  slowly  added  to  100  grm.  of  molten  benzoic  anhydride, 
and  the  whole  warmed  on  the  oil-bath  until  a  red  coloration 
appears.  The  melt  is  then  dissolved  in  water,  neutralised 
with  alkali,  and  acidified.  After  standing  for  a  few  days 
the  precipitate  is  collected,  boiled  with  water  and  animal 
charcoal,  and  the  filtrate  concentrated  on  the  water-bath  until 
crystallisation  sets  in. 

i  D.R.P.  225,232.  2  B.  17    1663. 


230      PREPARATION  OF  ORGANIC  COMPOUNDS 

Instead  of  using  methyl  iodide,  primary  and  secon- 
dary amines  are  usually  readily  methylated  by  dimethyl 
sulphate.  The  reaction  is  brought  about  by  heating 
the  amine  with  dimethyl  sulphate  alone,  or  more 
usually  in  the  presence  of  an  inert  solvent,  such  as 
nitrobenzene,  and  it  is  important  to  avoid  all  traces 
of  moisture.  This  is  best  achieved  by  boiling  the 
amine  alone  or  in  nitrobenzene,  &c.,  solution  for  a 
few  minutes  without  a  condenser  before  adding  the 
sulphate.  It  must  be  borne  in  mind  that  dimethyl 
sulphate  is  very  poisonous,  and  all  work  with  it  must 
be  carried  out  in  a  fume-chamber,  and  every  care 
taken  to  avoid  inhaling  any  of  its  vapour.  In  spite  of 
its  high  boiling-point  a  small  quantity  of  it  spilled  on 
the  clothing  has  been  known  to  cause  death.1  No 
remedy  is  known. 

PREPARATION     OF    w.-NITRO-MONOMETHYL  ANILINE 

(C6H4[i  ]NHCH3[3]NO2).2  Ten  grammes  of  dimethyl  sulphate 
are  heated  to  140°,  and  7  grm.  of  w.-nitraniline  added  little 
by  little,  the  whole  being  well  shaken  after  each  addition,  and 
the  temperature  maintained  at  I4O°-I5O°.  (Take  care!  See 
warning  above.)  After  cooling,  the  orange-coloured  mass  is 
diluted  with  ice-water,  and  then  10  c.c.  of  concentrated 
hydrochloric  acid  and  36  c.c.  of  10  per  cent,  sodium  nitrite 
added.  The  nitrosamine,  C6H4NO2N(NO)CH3  (M.P.  67°), 
separates  out,  and  is  collected  and  reduced  to  the  secon- 
dary base.  In  this  case  it  is  impossible  to  use  a  powerful 
reducing  agent,  such  as  zinc  dust  and  acids,  as  this  would  also 
reduce  the  nitro-group.  It  has  been  found,3  however,  that 
hydrochloric  acid  alone  is  capable  of  reducing  nitrosamines, 
and  this  is  the  best  method  when  there  is  danger  of  more 
powerful  reagents  attacking  other  groups  in  the  molecule.  The 
reduction  is  carried  out  simply  by  boiling  the  nitrosamine  with 
concentrated  hydrochloric  acid.  The  nitromethylaniline  is 
finally  purified  by  recrystallisation  from  alcohol  or  aqueous 
alcohol.  It  forms  reddish  yellow  needles  melting  at  66°. 

1  Archiv.  f.  Esperimentelle  Pathologic  und  Pharmakologie, 
47,  115  ;   127.     C.  1901,  i,  364. 

2  A.  327,   112. 

3  A.  128,  151  ;   B.  31,  2527. 


THE  AMINO-COMPOUNDS  231 

PREPARATION  OF  DIMETHYLANILINE  (C6H5N(CH3)2). 
Seventy-five  grammes  of  aniline,  25  grm.  of  aniline  hydro- 
chloride,  and  75  grm.  of  methyl  alcohol  are  heated  in  an  auto- 
clave or  in  sealed  tubes  for  eight  hours  to  240°.  The  product  is 
made  alkaline  with  caustic  soda  and  then  steam-distilled. 
The  oil  is  separated  from  the  aqueous  portion  of  the  distillate, 
dried  over  solid  caustic  potash,  and  then  fractionated.  The 
dimethylaniline  passes  over  between  190°  and  200°.  It  is  a 
colourless  liquid  which  rapidly  darkens.  B.P.  192°.  Its 
formation  in  the  above  preparation  is  probably  due  to  the 
intermediate  formation  of  methyl  chloride. 

2.   BY  HEATING  THE  PRIMARY  BASE  WITH 
ITS  HYDROCHLORIDE 

This  method  is  confined  to  the  preparation  of  secon- 
dary aromatic  bases,  and  is  that  used  technically  for 
the  preparation  of  diphenylamine. 

PREPARATION  OF  DIPHENYLAMINE,1  (C6H5)2NH. 
One  molecule  (93  grm.)  of  aniline  and  i£  molecules  (195  grm.) 
of  aniline  hydrochloride  are  heated  in  a  closed  vessel  for 
thirty-six  hours  to  230°.  The  product  is  extracted  with 
boiling  dilute  hydrochloric  acid  and  then  with  water.  The 
insoluble  portion  is  further  purified,  first  by  distillation,  and 
then  by  recrystallisation  from  ligroin.  Colourless  leaflets 
melting  at  54°,  and  boiling  at  310°. 

3.  BY   HEATING  THE   AMINES  WITH   IODINE 

A  very  general  method  for  preparing  diarylamines  in 
excellent  yield  has  been  the  subject  of  a  recent  patent.2 
It  consists  in  heating  the  primary  base,  or  a  mixture 
of  two  primary  bases,  or  a  mixture  of  a  primary  base 
and  a  phenol,  with  a  trace  of  iodine.  The  action  of  the 
iodine  is  catalytic  and  only  0-5  per  cent,  of  the  weight 
of  the  reaction  mass  is  required. 

PREPARATION  OF  /3/3-DINAPHTHYLAMINE,  (C10H7)2NH. 
One  hundred  grammes  of  /3-naphthylamine  and  0-5  grm.  of 
iodine  are  heated  for  four  hours  to  230°.  After  cooling,  the 

1  Z.  1886,  438.  2  D.R.P.  241,853. 


232      PREPARATION  OF  ORGANIC  COMPOUNDS 

melt  is  recrystallised  from  benzene.  M.P.  170° -171°.  The 
yield  is  almost  quantitative. 

PREPARATION  OF  PHENYL-/3-NAPHTHYLAMINE 

(C10H7NH.C6H6).  Seventy-two  grammes  of  /3-naphthol  and 
90  grm.  of  aniline  are  heated  with  I  grm.  of  iodine  for  seven 
hours  to  ioo°-i90°.  The  melt  is  boiled  out,  first  with  dilute 
hydrochloric  acid  and  then  with  dilute  caustic  soda.  The 
residue  is  dried  and  then  distilled  in  vacua.  The  phenyl 
naphthylamine  passes  over  in  almost  theoretical  yield  at  237° 
(15  mm.).  It  melts  at  108°. 

4.  BY  THE  REARRANGEMENT  OF  THE  OXIMES 

(Beckmann  Change) 

The  oximes  on  treatment  with  acids,  acid  chlorides 
(especially  phosphorus  pentachloride) ,  or  acid  anhy- 
drides undergo  a  remarkable  change  and  become  acid 
amides  : 

R.C— R'        R— C— OH        Tautomeric        R— C  =  O 

II.      —          II  | 

N— OH  N— R'  change  NHR' 

REARRANGEMENT  OF  BENZOPHENONE  OXIME.      One 

molecular  portion  of  phosphorus  pentachloride  is  dissolved  in 
twice  its  weight  of  phosphorus  oxychloride,  and  then  slowly 
added  to  one  molecular  proportion  of  benzophenone  oxime,  the 
whole  being  well  cooled  with  ice.  When  all  the  chloride  has  been 
added,  the  whole  is  allowed  to  stand  until  a  pale  yellow  preci- 
pitate has  settled  out  from  a  clear  yellow  liquid.  When  this 
has  taken  place  the  phosphorus  oxychloride  is  removed  by 
distillation  in  vacua  from  the  water-bath.  When  no  more 
phosphorus  chloride  passes  over,  a  few  cubic  centimetres 
of  petroleum  ether,  which  has  been  dried  over  sodium,  are 
added,  and  the  whole  again  distilled  in  vacuo.  This  process 
is  repeated  until  phosphorus  compounds  can  no  longer  be 
detected  in  the  distillate.  Without  allowing  the  residue  to 
cool,  it  is  mixed  with  8  parts  of  dry  petroleum  ether,  and  shaken 
until  a  semi-solid  precipitate  separates  out.  The  solution  is 
then  carefully  poured  off,  and  evaporated  by  distillation  under 
reduced  pressure.  Benzophenone- imide  chloride,  (C6H5)2C  : 
NCI,  is  left  as  a  crystalline  mass  melting  at  41°.  It  is  shaken 
up  with  90  per  cent,  alcohol,  made  alkaline  with  caustic  soda, 


THE  AMINO-COMPOUNDS  233 

and  the  solution  then  diluted  with  water.  The  benzanilide 
which  separates  is  recrystallised  from  absolute  or  aqueous 
alcohol.  M.P.  163°. 

ADDENDA 

A  class  of  tertiary  amines  is  obtained  by  the  action 
of  aldehydes  on  primary  amines  : 

R.CHO  +  H2NR  =  RCH  :  NR'  +  H2O. 

These  are  very  readily  decomposed  into  the  amine 
and  aldehyde,  and  are  useful  for  isolating  aldehydes 
(p.  108).  Their  formation  also  forms  a  ready  means  of 
"  protecting  "  the  amino-group  during  nitration,  for 
which  purpose  the  compounds  obtained  from  benzal- 
dehyde  (the  benzylidine  derivatives)  are  usually 
chosen. 

PREPARATION  OF  SODIUM  BENZYLIDENE  NAPH- 
THIONATE  (SO3Na[i]C10H6[4]N  :  CHC6H5).i  Twelve  grammes 
of  sodium  naphthionate  are  dissolved  in  60  c.c.  of  warm 
water,  and  3  grm.  of  benzaldehyde  dissolved  in  3  c.c.  of 
alcohol  added.  The  whole  is  well  shaken,  and  on  cooling 
yellow  leaflets  separate  (6|-  grm.).  These  are  collected,  and 
by  adding  more  benzaldehyde  to  the  nitrate  a  further  quantity 
can  be  obtained.  The  crystals  contain  one  molecule  of  water, 
which  they  lose  at  i4o°-i5O°. 

UREA.  Urea  is  the  amide  of  carbonic  acid,  and  is 
most  readily  obtained  by  the  intramolecular  rearrange- 
ment of  ammonium  cyanate  : 

NH4CNO    —     CO(NH2)2. 

The  rearrangement  takes  place  very  readily  on 
merely  evaporating  the  aqueous  solution  of  the  salt, 
and  is  reversible  at  a  higher  temperature. 

PREPARATION  OF  UREA  (CARBAMIDE)  (CO(NH2)2). 
Twenty  grammes  of  potassium  cyanide  are  dissolved  in 
300  c.c.  of  water,  and  a  solution  of  33  grm.  of  potassium 
permanganate  in  i  litre  of  water  slowly  run  in  during  an 

1  A.  247,  325  :    B.  20,  2002. 


234      PREPARATION  OF  ORGANIC  COMPOUNDS 

hour.  During  the  process  the  temperature  must  be  kept..  at 
about  5°,  and  the  whole  must  be  well  agitated.  This  is  best 
done  by  blowing  or  sucking  air  through  the  solution,  the 
oxygen  assisting  the  oxidation.  Manganese  dioxide  is  then 
removed  by  nitration,  and  any  excess  of  permanganate 
destroyed  by  adding  a  little  sulphurous  acid.  The  solution 
is  again  filtered,  35  grm.  of  ammonium  sulphate  added 
to  the  filtrate,  and  the  whole  taken  to  dryness  on  the  water- 
bath.  The  residue,  which  consists  chiefly  of  urea  and  potassium 
sulphate,  is  repeatedly  extracted  with  small  quantities  of 
boiling  alcohol  until  a  sample  of  the  extract  leaves  very  little 
residue  when  evaporated  to  dryness.  On  concentrating  the 
alcoholic  extracts,  the  urea  separates  out  as  colourless  prisms 
which  melt  at  132°. 

3KCN  +  H20  +  2KMn04  -  2KOH  +  2MnO2  +  3KCNO. 

2KCNO  +  (NH4)2SO4  =  K2SO4  +  2NH4CNO. 

NH4CNO  =  CO(NH2)2. 

The  syw-disubstituted  ureas  are  obtained  by  the 
action  of  carbonyl  chloride  on  the  primary  amines. 
Those  obtained  from  ^.-phenylenediamine  and  from 
the  amino-naphthol  sulphonic  acids,  especially  J-acid 
(NH2.OH.SO3H.i.5.7),  are  of  considerable  technical 
value  as  they  form  azo-colours  which  are  substantive 
to  cotton,  i.e.  dye  cotton  without  a  mordant.  The 
simplest  of  these  is  Cotton  Yellow  G  : 


The  Benzo  Fast  Scarlets,  however,  are  of  greater  im- 
portance. They  are  obtained  by  coupling  the  urea 
derived  from  J-acid  with  diazo-compounds. 

THE  THIOAMIDES  AND  THIOANILIDES.  With 
the  exception  of  the  thioureas,  the  thioamides  and 
thioanilides  are  fairly  readily  obtained  by  heating  the 
corresponding  oxygen  compounds  with  phosphorus 
pentasulphide.  In  preparing  the  thioamides  it  is 


THE  AMINOCOMPOUNDS  235 

necessary  to  use  a  large  volume  of  some  inert  solvent, 
such  as  benzene,  as  otherwise  the  phosphoric  oxide 
formed  during  the  reaction  will  react  with  the  amide 
to  form  a  nitrile  : 

R.CO.NH2    —     R.CN-f-H2O. 

PREPARATION  OF  THIOUREA  (THIOCARB  AMIDE).  One 

hundred  grammes  of  ammonium  thiocyanate  are  heated  to 
145°  for  six  hours.  The  melt  is  ground  up  and  unchanged 
thiocyanate  extracted  with  about  50  c.c.  of  cold  water.  The 
residue  is  then  recrystallised  from  hot  water.  It  forms 
colourless  prisms  or  needles  melting  at  172°.  Yield  about 
15  grm. 

/NH2  /NH 

N=C—  S—  NH4    -*     NH  =  C/  or  S  =  C/ 


The  rearrangement  is  exactly  analogous  to   that  undergone 
by  ammonium  cyanate,  and  is  also  reversible. 

PREPARATION  OF  sym  -  DIPHENYLTHIOURE  A 
(THIOCARBANILIDE)  (CS(NHC6H5)2).i  Fifty  grammes  of 
aniline,  50  grm.  of  alcohol,  50  grm.  of  carbon  bisulphide,  and 
0-25  grm.  of  crystallised  sulphur  are  boiled  on  the  water-bath 
for  six  hours  under  a  reflux  condenser.2  The  carbon  bisulphide 
is  then  removed  by  distillation,  the  residue  washed  free  of  aniline 
by  dilute  hydrochloric  acid,  and  then  recrystallised  from  dilute 
alcohol.  Colourless  plates.  M.P.  151°.  Yield  almost  theo- 
retical. 

/NH.C6H5 

CS2  +  2C6H5NH2  =  q=S  +  H2S. 

\NH.C6H6 

The  above  method  is  of  very  general  application  for 

1  Fischer,    "Anleitung    zur    Darst.  organ.    Prep."    (1905), 
p.  7. 

2  Carbon  bisulphide  is  very  highly  inflammable,  and  care 
must  be  taken  not  to  bring,  a  light  near  it.     In  the  above 
experiment  steam,  if  available,  is  the  best  source  of  heat. 
If  steam  is  not  available,  a  large  bucket  of  hot  water,  which 
is  renewed  from  time  to  time,  can  be  used.     It  is  not  safe  to 
heat  the  water-bath  directly  by  a  flame. 


236      PREPARATION  OF  ORGANIC  COMPOUNDS 

the  preparation  of  sym-diaryl  thioureas  from  primary 
aromatic  amines  with  the  exception  of  the  amino- 
anth/aquinones.  The  sulphur  acts  as  a  catalyst  and 
greatly  facilitates  the  reaction. 

Like  the  corresponding  ureas,  the  syw-diaryl  thio- 
ureas give  direct  cotton  azo-colours.  Thus  the  thio- 
urea  derived  from  ^.-phenylenediamine  when  diazo- 
tised  and  coupled  with  sodium  naphthionate  gives 
Salmon-red.  Some  of  the  Benzo  Fast  Scarlets  are  azo- 
dyes  obtained  by  coupling  diazo-compounds  with  the 
thiourea  derived  from  J-acid. 

PREPARATION  OF  THIOACET AMIDE  (CH3.C^NH2).i 
Five  molecules  of  acetamide  and  one  molecule  of  finely 
powdered  phosphorus  pentasulphide  are  boiled  under  a  reflux 
condenser  with  a  large  excess  (about  50  parts)  of  benzene  for 
twenty  minutes.  The  solution  is  then  filtered,  and  concentrated 
until  the  thioamide  crystallises  out.  Yellow  prisms  (from 
ether)  melting  at  iO7°-io8°. 

The  thioamides  can  also  be  conveniently  prepared 
by  treating  the  alcoholic  solution  of  the  nitrile  with 
hydrogen  sulphide  in  the  presence  of  ammonia,  e.g. : 
C6H5CN  +  H2S  =  C6H5CSNH2. 

PREPARATION  OF  THIOBENZANILIDE  (C6H5NH. 
CS.C6H5).2  Twenty  grammes  of  benzanilide  are  intimately 
mixed  with  10  grm.  of  finely  powdered  phosphorus  penta- 
sulphide and  10  grm.  of  finely  powdered  phosphorus  trisulphide. 
The  whole  is  then  cautiously  heated  over  a  naked  flame  with 
continual  shaking  until  fusion  takes  place,  and  the  melt  takes 
a  yellow  colour.  After  cooling,  the  whole  is  extracted  several 
times  by  boiling  with  alcohol  or  acetone,  the  united  extracts 
made  strongly  alkaline  with  caustic  soda,  and  then  poured 
into  a  large  bulk  of  water.  The  dark  coloured  solution 
obtained  on  filtration  is  then  saturated  with  carbon  dioxide, 
when  the  thiobenzanilide  separates  as  a  yellow  crystalline 
precipitate  which  does  not  require  further  purification.  It 
melts  at  97°-98°.  The  yield  is  about  90  per  cent. 
1  A.  250,  264.  2  Proc.  27,  8. 


CHAPTER  XI 

THE  DIAZO-,  DIAZOAMINO-,  DIAZOIMINO,-  AZO-, 
AZOXY-,    AND    HYDRAZO-COMPOUNDS 

I.     THE  DIAZO-COMPOUNDS 

THE  true  diazo-compounds  contain  the  group,  Ar.N  = 
NAc,  where  Ac  is  an  inorganic  or  organic  acyl  group, 
or  a  halogen  atom,  and  Ar  is  an  aromatic  group.  The 

N\     / 
fatty  diazo-compounds  contain  the  structure  ||    )C\ 

N/ 
and  are  of  very  minor  importance. 

The  aromatic  diazo-compounds  are,  as  a  rule, 
dangerously  explosive  in  the  dry  state,  diazo- 
benzene  nitrate  exploding  with  even  greater  violence 
than  mercury  fulminate.  Hence,  in  preparing 
derivatives,  such  as  the  azo-dyes,  it  is  usual  merely 
to  work  with  the  aqueous  solution  or  suspension  of 
one  of  the  salts,  usually  the  chloride.  Some  of  the 
diazo-compounds,  however,  are  quite  stable.  Thus 
the  diazo-salts  derived  from  i-naphthol-2-amino-4- 
sulphonic  acid  can  be  nitrated  and  sulphonated,  and 
the  diazo-sulphate  of  ^.-nitraniline  is  an  article  of 
commerce,  being  used  in  conjunction  with  /3-naphthol 
in  the  preparation  of  Para-red,  an  insoluble  dyestuff 
produced  directly  on  the  fibre. 

The  only  practical  method  of  preparing  diazo- 
compounds  is  the  action  of  nitrous  acid  on  the  primary 
aromatic  amines  : 

Ar  .NH2  +  HO  .NO  +  HC1  =  ArN  :  N  .Cl  +  2H2O. 

If  it  is  desired  to  isolate  a  water-soluble  diazo-salt, 

237 


238      PREPARATION  OF  ORGANIC  COMPOUNDS 

the  primary  amine  is  dissolved  in  alcohol,  acid  added, 
and  then  the  calculated  quantity  of  amyl  nitrite  slowly 
run  in,  the  temperature  being  kept  at  about  5°.  The 
diazo-compound  is  then  precipitated  with  ether.  Thus 
when  50  grm.  of  aniline  hydrochloride  are  dissolved  in 
150  c.c.  of  alcohol  and  treated  with  65  grm.  of  amyl 
nitrite  at  a  temperature  below  10°,  53  grm.  of  diazo- 
benzene  chloride  can  be  obtained  by  precipitating  the 
reaction  mixture  with  ether. 

In  almost  all  cases,  however,  the  diazotisation  is 
carried  on  in  aqueous  solution  with  nitrous  acid.  For 
this  purpose  one  molecule  of  the  amine  is  dissolved 
or  suspended  in  10  to  20  parts  of  cold  water  con- 
taining 2%  ^0  3  molecules  of  mineral  acid  (usually 
hydrochloric  acid),  the  solution  cooled  to  5°  by  the 
direct  addition  of  ice,  and  an  aqueous  solution  of 
one  molecule  of  sodium  nitrite  *  run  in  slowly  with 
continual  stirring,  rise  in  temperature  being  prevented 
by  adding  more  ice  from  time  to  time.  After  all  the 
nitrite  has  been  added  the  stirring  is  continued  for 
ten  minutes,  after  which  time  the  solution  should  give 
a  faint  reaction  with  starch-iodide  paper.  If  no  reaction 
is  obtained,  a  little  more  nitrite  must  be  added ;  if  a 
strong  reaction  is  obtained,  a  little  more  of  the  base. 

Under  these  conditions  the  base  is  usually  quanti- 
tatively converted  into  its  diazo-salt,  which  in  most 
cases  remains  in  solution,  and,  if  desired,  can  often  be 
precipitated  by  the  addition  of  a  suitable  salt,  such 
as  sodium  picrate  or  sodium  dichromate,2  the  diazo- 

1  Commercial  sodium  nitrite  contains  about  98  per  cent,  of 
NaNO2  and  is  slightly  deliquescent.     It  can  be  conveniently 
replaced  by  barium  nitrite,  which,  although  exceedingly  soluble 
in  water,  is  not  in  the  least  hygroscopic,  and  can,  therefore,  be 
weighed  out  accurately.     The  use  of  barium  nitrite  has  the 
advantage  that  all  inorganic  matter  can  be  removed  from  the 
solution  by  adding  the  calculated  quantity  of  sulphuric  acid, 
or  a  slight  excess  of  sulphuric  acid  and  then  barium  carbonate. 
This  is  a  great  advantage  when  it  is  desired  to  isolate  the 
diazo-salt  by  precipitation  with  alcohol  and  ether. 

2  Bl.  j>]  7,  270  ;   P.P.  73,286. 


THE  DIAZO-,  ETC.,   COMPOUNDS  239 

picrate  or  chr ornate  separating  out.  In  some  cases, 
e.g.  diazotised  ^.-aminobenzanilide,  even  the  carbonate 
can  be  obtained  by  this  method.  *  Some  diazo-chlorides, 
however,  notably  those  of  sulphanilic  and  naphthionic 
acids,  are  insoluble  in  water  and  separate  out.  These 
can,  if  desired,  be  filtered  off,  but  must  on  no  account  be 
allowed  to  dry,  as  they  are  very  explosive. 

If  the  amine  to  be  diazotised  is  difficultly  soluble  in 
cold  dilute  acids,  it  should  be  dissolved  boiling,  and  the 
solution  then  cooled  as  rapidly  as  possible,  with 
violent  agitation,  in  order  that  the  base  may  separate 
out  in  a  finely  divided  state.  Amino-sulphonic  or 
carboxylic  acids  are  best  dissolved  in  alkali,  and  then 
reprecipitated  by  acids.  Bases  which  are  only  attacked 
by  nitrous  acid  with  difficulty  can  often  be  successfully 
diazotised  by  dissolving  in  concentrated  sulphuric 
acid,  and  a  concentrated  solution  of  sodium  nitrite 
then  run  in  very  slowly  at  a  temperature  of  —  15°  ; 
or  solid  sodium  nitrite  or  its  solution  in  concentrated 
sulphuric  acid  (nitrosyl  sulphuric  acid)  can  be  used. 

It  will  be  noticed  in  the  above  directions  that  a 
large  excess  of  acid  is  always  employed.  This  is 
necessary  in  order  to  prevent  the  formation  of  diazo- 
amino  compounds : 

Ar.N2.Cl  +  HNHAr  =  ArN2.NH.Ar. 

If  an  organic  acid,  such  as  acetic  acid,  is  used  in 
place  of  mineral  acid,  a  very  large  excess  is  required. 
Thus  a  i  per  cent,  solution  of  aniline  diazotised  in  the 
presence  of  2-J-  molecules  of  acetic  acid  gave  only 
19-20  per  cent,  of  diazobenzene  acetate,  and  quan- 
titative yields  could  only  be  obtained  when  36  molecules 
of  acetic  acid  were  used.  The  tendency  to  form 
diazoamino-compounds  differs  considerably  with  the 
different  amines,  and  in  cases  where  the  tendency  is 
great,  as,  for  example,  with  />.-nitraniline,  the  whole 
of  the  nitrite  must  be  added  at  once. 

DIAZOTISATION  OF  £.-NITRANILINE.     Seven  grammes  of 
/?.-nitraniline  are  dissolved  by  boiling  with  20  c.c.  of  concen- 
1  Soc.  87,  921. 


24o      PREPARATION  OF  ORGANIC  COMPOUNDS 

trated  hydrochloric  acid  and  20  c.c.  of  water.  After  cooling, 
the  whole  is  poured  into  200  c.c.  of  water  and  ice  then 
added  until  the  temperature  falls  to  10°.  A  concentrated 
solution  of  3  -6  grm.  sodium  nitrite  is  then  added  all  at  once, 
the  whole  being  vigorously  stirred.  No  precipitation  of  the 
diazoamino-compound  should  take  place. 

Although  the  directions  given  above  are  of  very 
general  application,  there  are  cases  to  which  they 
are  not  applicable.  Thus  w.-phenylenediamine  when 
diazotised  in  the  ordinary  way  gives  Bismarck  brown, 
one  molecule  being  tetrazotised  and  then  coupling  with 
two  molecules  of  the  unchanged  base  : 


C6H4(N2C1)2+2C6H4(NH2)2      -,     C6H4 


The  base,  however,  can  be  tetrazotised  by  a  special 
procedure. 

TETRAZOTISATION       OF       m.-PHENYLENEDIAMINE.i 

Eighty  cubic  centimetres  of  concentrated  hydrochloric  acid 
are  diluted  with  320  grm.  of  ice,  and  the  whole  well  cooled  in 
a  freezing  mixture.  A  strong  aqueous  solution  of  15  grm.  of 
sodium  nitrite  is  added  and  then,  as  rapidly  as  possible,  a  cold 
aqueous  solution  of  9  grm.  w.-phenylenediamine  hydrochloride 
to  which  i  c.c.  of  concentrated  hydrochloric  acid  has  been 
added.  During  the  addition  of  the  diamine  the  solution  must 
be  well  stirred. 

o.-Phenylenediamine  cannot  be  diazotised,  as  it 
forms  an  azoimino-derivative  :  2 

/N 
C6H  /  [  >NH 

\N/ 

^.-Phenylenediamine  gives  a  mixture  of  the  diazo- 
and  tetrazo-derivatives,  and,  therefore,  its  technically 
important  diazo-derivatives  must  be  prepared  in  two 
steps.  For  this  purpose  either  ^.-nitraniline  is 

1  B.  30,  93,  2203,   2899  ;    D.R,P,   103,660. 

2  B.  9,  221. 


THE  DTAZO-,  ETC.,  COMPOUNDS  241 

diazotised  (p.  239),  and  then  coupled  with  a  phenol, 
the  nitro-group  reduced  with  ammonium  sulphide, 
and  the  resulting  aminoazo-compound  again  diazotised 
and  coupled  : 

N02C6H4.NH2  —  N02.C6H4.N2C1  —  NO2 .  C6H4N2 .  Ar 

ArN2.C6H4.N2Ar  *-  N2C1 . C6H4N2 Ar  —  NH2.C6H4N2Ar 

(see  p.  253)  ;  or  monoacetyl-/>.-phenylenediamine  is 
diazotised  and  coupled,  the  acetyl  group  split  off,  and 
the  primary  amine  thus  obtained  again  diazotised  and 
coupled. 

Nitro-groups  in  the  ortho-  or  para-  position  often 
protect  amino-groups  from  the  action  of  nitrous  acid. 
Thus  when  mononitro-^.-phenylenediamine : 


NH, 


is  treated  with  nitrous  acid,  only  the  amino-group  at 
4  is  attacked.  If,  however,  the  diazo  -  compound 
thus  obtained  is  coupled,  the  resulting  aminoazo- 
compound  is  readily  diazotised.  The  amino-group  at 
i  is  also  readily  diazotised  if  the  group  at  4  is  first 
acetylated.  The  sulphonic  group  exerts  an  influence 
similar  to  that  of  the  nitro-group. 

Benzidine,  &c.,  cannot  be  diazotised,  but  is  readily 
tetrazotised.  In  order  to  obtain  the  diazo-compound 
one  amino-group  must  first  be  protected  by  acetylation, 
or  a  molecular  mixture  of  tetrazotised  benzidine 
and  benzidine  is  allowed  to  stand  for  three  days  : 

C1N2C6H4.C6H4.N2C1  +  H2N.C6H4.C6H4.NH2  - 
2NH2.C6H4.C6H4.N2C1. 

The  amino-naphthols,  in  which  the  amino-  and 
hydroxy -groups  are  in  the  ortho-  (1.2)  positions  to  each 
other,  are  oxidised  by  nitrous  acid  to  the  correspond- 

16 


242      PREPARATION  OF  ORGANIC  COMPOUNDS 

ing  /S.-naphthoquinones.  This  oxidation,  however, 
can  be  prevented  by  carrying  out  the  diazotisation  in 
the  presence  of  copper,1  mercury,  zinc,  iron,  or  nickel 
salts.  When  this  procedure  is  adopted  only  one 
equivalent  of  mineral  acid  is  used.  When  an  amino- 
naphthol  sulphonic  acid  is  to  be  diazotised,  no  acid  is 
added,  the  sulphonic  group  liberating  the  nitrous  acid. 
The  amino-naphthols  can  also  be  diazotised  by  replacing 
the  mineral  acid  by  acetic,  oxalic,  tartaric,  or  phthalic 
acid. 

DIAZOTISATION  OF  I-AMINO-2-NAPHTHOL-4-SUL- 
PHONIC  ACID.  (a)2  Twenty-four  grammes  of  the  acid  are 
dissolved  in  about  500  c.c.  of  water  containing  one  equivalent 
of  sodium  acetate  or  carbonate.  Two  hundred  grammes  of 
30  per  cent,  acetic  acid  are  then  added,  and  the  whole  cooled 
to  io°-is°.  Sodium  nitrite  solution  is  then  added  very  slowly 
(several  hours  will  be  required)  to  the  well-stirred  solution 
until  a  permanent  reaction  is  obtained  with  starch- iodide  paper. 

(b)  3  Twelve  grammes  of  the  acid  are  made  into  a  paste  with 
50  c.c.  of  water  containing  i  grm.  of  crystallised  copper  sul- 
phate. A  concentrated  aqueous  solution  of  3-5  grm.  of 
sodium  nitrite  is  then  added  very  slowly  to  the  well-stirred 
liquid,  the  temperature  being  maintained,  at  io°-i5°. 

DIAZOTISATION  OF  a-AMINO-/3-NAPHTHOL.4  Twenty 
grammes  of  the  hydrochloride  are  dissolved  in  1500  parts  of 
water,  containing  5  parts  of  copper  sulphate,  and  the  diazo- 
tisation brought  about  by  the  very  slow  addition  of  8  grm.  of 
sodium  nitrite  in  500  c.c.  of  water.  During  the  diazotisation 
the  temperature  should  not  exceed  8°. 


II.  THE  DIAZOAMINO-COMPOUNDS 

The  diazoamino  -  compounds  contain  the  group 
Ar.N:N.NHR,  and,  as  was  pointed  out  on  p.  239, 
are  formed  by  the  union  of  one  molecule  of  a  diazo- 
salt  with  one  molecule  of  a  base.  Since  diazobenzene 
chloride  and  ^.-toluidine,  and  diazo-^.-toluene  chloride 

1  D.R.P.  155,083,  171,024,  172,446,  175,593,  176,618-19-20. 

2  D.R.P.   155,083. 

3  D.R.P.  171,024.  4  D.R.P.  172,446. 


THE  DIAZO-,  ETC.,   COMPOUNDS  243 

and  aniline  give  the  same  compound,  it  is  probable 
that  an  addition  compound  is  first  formed,  which  then 
loses  hydrochloric  acid  : 

|H Cii  H 

C6H5N  :  N.C1  +  C7H7NH2      -»        C6H5N— N— N— C7H7 

I 
C6H5N  =  N— NH .  C7H7 

The  combination  of  the  diazo-salt  with  the  base 
takes  place  in  neutral  or  faintly  acid  solution,  and  is  in 
many  cases  accompanied  by  the  simultaneous  formation 
of  an  aminoazo-compound.  Thus  the  benzene  mon- 
amines  usually  give  almost  quantitative  yields  of 
diazoamino-compounds,  but  diazotised  sulphanilic 
acid  and  monomethyl  aniline  give  a  mixture  of  diazo- 
amino-compound  and  azo-dye.  The  diphenylamines 
and  naphthylamines,  on  the  other  hand,  give  only  the 
azo-compound,  the  diazoamino-compound  only  being 
obtained  by  splitting  out  water  between  a  molecule 
of  the  nitrosamine  and  a  molecule  of  a  primary  base : 

Ar .  NH .  N  :  p H^N Ar    —     Ar .  NH .  N  :  N Ar 

or  by  the  action  of  Grignard's  reagent  on  the  diazo- 
imides.1  In  order  to  prepare  a  diazoamino-compound 
by  the  interaction  of  a  diazo-salt  on  a  base,  several 
procedures  can  be  adopted.  Thus  one  molecule  of  the 
base  can  be  diazotised  in  the  ordinary  way  and  then 
mixed  with  a  molecule  of  the  same  or  other  suitable 
base,  and  sodium  acetate  then  added  until  no  more 
mineral  acid  is  present  (test  with  Congo  paper) .  Under 
these  conditions  the  diazoamino-compound  separates 
out,  and  after  standing  for  a  time  is  filtered  off.  Or 
two  molecules  of  the  hydrochloride  of  the  base  are 
diazotised  with  one  molecule  of  sodium  nitrite  in 
the  absence  of  free  mineral  acid,  the  diazoamino- 
compound  being  continually  formed  during  the  process. 
A  third  variation,  not  often  adopted,  is  to  pass  gaseous 
nitrous  acid  into  an  alcoholic  solution  of  the  base. 

1  B.  36,  909  ;  38,  670  ;  40,  2390. 


244      PREPARATION  OF  ORGANIC  COMPOUNDS 

Mixed  diazoamino-compounds  can  be  obtained  by 
allowing  a  diazo-solution  to  act  on  an  aliphatic  amine 
according  to  the  first  of  the  above  methods.  Under 
these  circumstances,  however,  only  benzylamine  reacts 
smoothly,  there  being  a  great  tendency  to  form 
disdiazoamino-compounds,  (ArN2)2NR,  in  the  case 
of  methylamine,  ethylamine,  &c.  This  can  be  avoided 
by  accurately  neutralising  the  diazo-solution  with 
sodium  carbonate,  and  then  adding  it  to  the  aqueous 
solution  of  the  base  mixed  with  ice  and  sodium  car- 
bonate and  covered  with  ether.  The  ether  takes  up 
the  diazoamino-compound  as  soon  as  it  is  formed, 
and  thus  protects  it  from  being  further  attacked  by 
the  diazo-solution. 

PREPARATION  OF  DIAZOAMINOBENZENE  (C6H5N  : 
N .  NH . C6H5)  .*  Ten  grammes  of  aniline  are  dissolved  in  100  c.c. 
of  cold  water  and  30  c.c.  of  concentrated  hydrochloric  acid, 
the  solution  cooled  to  2°  by  adding  ice,  and  then  diazotised  by 
running  in  slowly  a  solution  of  8  grm.  of  sodium  nitrite  in 
50  c.c.  of  water.  During  the  diazotisation  the  solution  should 
be  well  stirred,  and  rise  in  temperature  prevented  by  adding 
more  ice  from  time  to  time.  An  ice-cold  solution  of  14  grm. 
of  aniline  hydrochloride,  or  of  10  grm.  of  aniline  and  the 
calculated  quantity  of  hydrochloric  acid,  in  50  c.c.  of  water 
is  then  added  to  the  diazo-solution,  and  finally  a  concentrated, 
ice-cold  solution  of  50  grm.  of  sodium  acetate.  After  stirring 
for  half  an  hour  the  diazoamino-benzene  is  filtered  off,  washed 
with  water,  dried  between  filter-paper,  and  recrystallised  from 
petroleum  ether  or  alcohol.  It  forms  yellow  plates  which 
melt  at  98°  and  explode  at  higher  temperatures.  The  yield  is 
quantitative. 

PREPARATION  OFN.-METHYL  DIAZOAMINOBENZENE- 
/>.-SULPHONIC  ACID  (C^N .  (CH3)N2 .  C6H4SO3H)  .2  Seventy- 
seven  grammes  of  the  sodium  salt  of  sulphanilic  acid  are  dis- 
solved in  3500  c.c.  of  water  containing  36  grm.  of  sulphuric 
acid.  The  solution  is  cooled  to  5°  by  adding  ice,  and  then 
diazotised  by  the  slow  addition  of  24  grm.  of  sodium  nitrite 
in  750  c.c.  of  water.  The  diazo-solution  thus  obtained  is  run 

1  Gattermann,  " Praxis  der  organ.  Chemikers  "  (1909),  p.  246. 

2  B.  20,  925. 


THE  DIAZO-,  ETC.,  COMPOUNDS  245 

slowly  into  a  well-cooled  solution  of  40  grm.  of  monomethyl 
aniline  in  2500  c.c.  of  water  and  40  c.c.  of  concentrated  hydro- 
chloric acid,  sodium  acetate  or  caustic  soda  being  added 
simultaneously  so  as  to  keep  the  reaction  mixture  as  nearly 
neutral  (litmus)  as  possible.  This  is  important,  and  the  solu- 
tion must  not  be  allowed  to  become  alkaline.  When  the  whole 
of  the  diazo-solution  has  been  added,  the  azo-dye  and  the 
diazoamino-compound  are  salted  out  as  their  sodium  salts  by 
saturating  the  solution  with  common  salt.  The  precipitate 
is  filtered  off  and  washed  with  brine.  In  order  to  get 
rid  of  the  azo-dye,  the  whole  is  dissolved  in  concentrated 
ammonium  sulphide  solution  by  warming  on  the  water -bath, 
and  the  warming  continued  for  some  time.  After  cooling,  the 
brown-coloured  solution  is  allowed  to  stand  for  a  day  or  two, 
when  it  deposits  grey  leaflets.  These  are  collected,  washed, 
and  recrystallised  from  hot  water,  when  they  should  separate 
colourless. 

The  action  of  the  ammonium  sulphide  is  to  split  the  azo- 
linkage  in  the  aminoazo  -  compound  formed  by  a  side- 
reaction  : 

NHMe.C6H4.N2.C6H4SO3Na  +  4H  = 

,NMeH  yNH2 

CeH4v  +  C6H4. 

\NH2  \S03Na 

The  aromatic  disdiazoamino  -  compounds,  (ArN2),j 
NAr,  are  best  prepared  by  combining  two  molecules 
of  the  diazo-chloride  with  one  molecule  of  the  primary 
base  in  alkaline  alcoholic  solution.1 


III.    THE  DIAZOIMIDES 

/^ 
The  diazoimides  contain  the  group   R.NC  ||    and 

are  often  known  as  triazo-compounds.  They  may  be 
regarded  as  organic  derivatives  of  hydr azoic  acid, 
and  can  be  obtained  by  the  action  of  sodium  azide  on 
the  corresponding  diazo-salt  or  halogen  compound.2 
As  a  rule,  however,  they  are  prepared  (a)  by  the  action 

1  B.  27,  705.  2  Soc.  91,  1942,  &c.  ;    B.  26,  86. 


246      PREPARATION  OF  ORGANIC  COMPOUNDS 

of  nitrous  acid  on  the  hydrazines,  the  nitroso-compound 
first  formed  readily  losing  water  on  gently  warming  : 

HNO2  — H2O 

Ar.NH.NH2     —     Ar.N— NH2     —     Ar.N— N 

I  \/ 

NO  N 

or  (b)  by  the  action  of  the  diazo-salt  on  hydroxyl- 
amine  :  1 

R.N:N.HSO4  +  NH2OH  — >  R.N— N.HSO4  —  R.N  — N 

I        I  \/ 

NH2  OH  N 

If  negative  groups  are  present  it  is  best  to  replace 
the  hydroxylamine  by  potassium  hydroxylamine 
mono-  or  disulphonate.  Thus  ^.-nitrobenzene  diazo- 
chloride,  treated  in  the  cold  with  2^  molecules  of  potas- 
sium hydroxylamine  sulphonate,  gives  an  almost 
quantitative  yield  of  ^.-nitro-diazobenzeneimide.2 

The  diazoimides  can  also  be  obtained  by  the  action 
of  the  diazo-salt  on  the  hydrazines.3 

PREPARATION       OF      DI AZOBENZENEIMIDE, 

/N 
C6H5.N^  ||      Thirty  grammes  of  phenylhydrazine  are  mixed 

\N 

with  400  c.c.  of  water  containing  45  c.c.  of  concentrated 
hydrochloric  acid.  The  mixture  is  then  cooled  by  the  addition 
of  ice,  and  a  solution  of  sodium  nitrite  slowly  run  in  with 
continual  stirring  until  a  permanent  reaction  is  obtained  with 
starch-iodide  paper  (about  24  grm.  of  nitrite  will  be  required). 
The  diazoimide  separates  out  as  an  oil.  The  greater  portion 
of  the  water  is  then  siphoned  off,  the  oil  extracted  from  the 
residue  with  ether,  the  ether  removed  by  distillation  from  the 
water-bath,  and  the  residue  steam-distilled.  The  oil  is  extracted 
from  the  distillate  with  ether,  the  solution  dried  with  anhy- 
drous sodium  sulphate,  and  the  ether  removed  by  distillation. 
The  yield  is  about  70  per  cent.  Diazobenzeneimide  forms  a 
yellow  oil  with  a  stupefying  odour.  It  boils  at  59°  at  12  mm. 
If  heated  at  the  ordinary  pressure  it  explodes. 

1  B.  25,  372  ;  26,  1271.          2  B.  33,  3408. 

3  B.  20,  1528  ;  26,  1263  ;  33,  2746;  J.  pr.  [2],  66,  336. 


THE  DIAZO-,  ETC.,   COMPOUNDS  247 

IV.  THE  AZO-COMPOUNDS 

The  azo-compounds  contain  the  group  Ar  .N  =  N .  R, 
and  are  of  the  greatest  importance  as  forming  the 
valuable  azo-dyes.  As  the  methods  used  in  preparing 
the  compounds  differ  according  to  whether  a  hydroxyl 
or  an  amino-group  is  present  or  not,  they  will  be 
considered  in  two  groups. 

A.     Amino-  and  Hydroxyl  Groups  are  Absent. 

(i)  By  the  Reduction  of  the  Azoxy-Compounds.  This 
is  the  standard  method  of  preparing  the  azo-hydro- 
carbons,  the  reduction  being  effected  by  distillation 
over  iron  filings. 

PREPARATION  OF  AZOBENZENE  (C6H5.N  =  N.C6H5)  * 
Twenty  grammes  of  azoxy benzene  and  60  grm.  of  iron  filings, 
both  of  which  have  been  carefully  dried  on  the  water-bath, 
are  well  mixed  by  grinding,  and  are  then  carefully  distilled 
from  a  very  small  retort,  conveniently  made  by  blowing 
a  bulb  on  a  piece  of  wide  glass  tubing,  until  nothing  more 
distils  over.  The  distillate,  which  contains  traces  of  aniline, 
is  washed  with  a  little  dilute  hydrochloric  acid,  and  well 
pressed  between  filter-paper.  It  is  finally  purified  by  recrys- 
tallisation  from  ligroin,  in  which  it  is  very  soluble.  It  forms 
red  plates  melting  at  68°.  The  yield  is  70  per  cent. 

(ii)  By  the  Reduction  of  the  Nitro-Compounds.  The 
nitro-compounds  can  be  reduced  to  azo-compounds 
by  the  action  of  zinc  dust  and  alkali,  by  alkaline 
stannite  solution,  or  by  prolonged  heating  with  concen- 
trated caustic  soda  and  carbon  (coal).2  The  best 
yields,  however,  are  obtained  by  carrying  out  the 
reduction  electrolytically,3  the  nitro-compound  being 
dissolved  in  70  per  cent,  alcohol  containing  sodium 
acetate.  By  this  method  azobenzene  is  obtained  from 
nitrobenzene  in  90  per  cent,  yield. 

(iii)  By  the  Oxidation  of  the  Primary  Amines.  This 
method  is  not  much  employed,  but  is  useful  when 
several  side-chains  are  present.  The  oxidation  is 

1  A.  207,  329.  2  D.R.P.  210,806. 

3  B.  33,  2331.  See  also  Elb's  "  Electrolytic  Preparations," 
p.  78. 


248      PREPARATION  OF  ORGANIC  COMPOUNDS 

carried  out  with  alkaline  permanganate  or  potassium 
ferricyanide.1  The  hydrazo-compounds  can  also  be 
oxidised  to  the  azo-compounds  (mercuric  oxide  and 
ether),  and  this  method  is  useful  for  preparing  mixed 
azo-compounds  and  fatty  azo-compounds. 

(iv)  Mixed  Azo-Compounds  are  obtained  when  a 
diazo-salt  reacts  with  a  fatty  compound  containing  a 
reactive  hydrogen  atom,  such  as  acetoacetic  ester,2 
malonic  ester,  nitromethane,3  &c. 

(v)  Nitroso-Compounds  condense  with  primary  amines 
with  the  loss  of  water  to  form  azo-compounds  : 4 

R.Nj6T'H«iNR'    =   R.N  =  N.R'  +  H2O. 

B.   Amino-  or  Hydroxyl  Groups  are  Present. 

The  amino-azo  and  oxyazo-compounds  are  of  in- 
finitely greater  importance  than  the  above-mentioned 
azo-compounds,  and  although  most  of  the  above 
methods  are  applicable  to  their  preparation,  they  are 
usually  prepared  by  coupling  a  diazo-salt  with  a  phenol, 
phenolic  ether,  or  an  aromatic  amine. 

Ar.N:N.Cl  +  C6H5OH   =  ArN  :N.C6H4.OH+HC1. 

In  the  case  of  benzene  derivatives  the  azo-group 
enters  the  para-  position  to  the  amino-  or  oxy-group  if 
this  is  free.  If  the  para-  position  is  occupied  the  azo- 
group  takes  the  ortho-  position. 

In  the  naphthalene  series,  if  the  amino-  or  hydroxy- 
group  is  in  the  a-  position,  the  azo-group  takes  the 
para-  position  with  respect  to  it  unless  there  is  a  sul- 
phonic  acid  group  at  3,  4,  or  5,  in  which  case  the  ortho- 
position  is  taken.  If  the  amino-  or  hydr oxy-group 
is  in  the  /3-  (2)  position  the  azo-group  takes  the  a-  (i) 
position.  If  this  position  is  occupied  no  azo-compound 
is  formed.  Under  ordinary  circumstances,  dioxy-  and 
diamino-benzenes  only  couple  when  the  hydroxy-  and 
amino-groups  are  in  the  meta-  position  to  one  another 
("  Chrysoidine  law"),  but  the  ortho-  and  para-com- 
pounds will  couple  under  special  conditions. 

1  A.  142,  364  ;  B.  17,  476. 

2  B.  9,  384  ;  II,  1417  ;  17,  1926  ;  25,  746  ;  32, 197. 

3  B.  27,  155  ;  33,  2043,          4  B.  7,  1638. 


THE  DIAZO-,  ETC.,  COMPOUNDS  249 

As  a  rule,  only  one  azo-group  enters  the  molecule, 
but  a-naphthol  gives  an  azo-  and  a  disazo-compound, 
and  resorcinol  gives  an  azo-,  a  disazo-,  and  a  trisazo- 
compound.  Some  heterocyclic  compounds,  e.g. 
i-phenyl-3-methyl-5-pyrazalone,  also  couple  with  diazo- 
compounds.1 

The  oxyazo-compounds  are  formed  in  the  presence 
of  alkali,  and  are  obtained  by  slowly  adding  the  diazo- 
solution  to  a  solution  or  suspension  of  the  phenol  in 
caustic  alkali  or  alkali  carbonate,  care  being  taken  that 
excess  alkali  is  always  present.  Under  these  circum- 
stances, if  no  sulphonic  or  carboxylic  acid  groups  are 
present  in  either  component,  the  azo-compound  sepa- 
rates out  and  only  requires  to  be  filtered  off,  washed, 
and  recrystallised.  Such  products  are,  however,  useless 
as  dyestuffs,  owing  to  their  insolubility  in  water.2  If 
either  or  both  the  components  contain  the  sulphonic 
acid  group,  most  or  all  of  the  azo-colour  remains  in 
solution.  It  is  usually  isolated  by  heating  the  solution 
to  80°,  and  then  adding  sodium  chloride  slowly  until 
the  liquid  is  almost  saturated.  Under  these  conditions 
the  dyestuff  separates  out  more  or  less  completely  as 
its  sodium  salt,  and  is  filtered  off  hot.  Such  products 
are  usually  contaminated  with  considerable  quantities 
of  salt,  but  in  many  cases  the  dyestuff  can  be  dissolved 
out  and  recrystallised  by  extraction  with  alcohol.  In 
place  of  sodium  chloride  it  is  sometimes  advantageous 
to  use  potassium  chloride  ("  waste  salt  ")  or  calcium 
chloride.  Dyestuffs  which  are  very  soluble  and  do 
not  salt-out  well  are  sometimes  better  precipitated 
as  the  free  acid  by  adding  excess  of  hydrochloric 
acid.  Whether  this  method  or  the  usual  salting-out 
method  is  adopted,  the  dyestuff  should  not  be  made 
to  separate  too  rapidly,  as  if  this  is  done  it  will  probably 
form  a  colloidal  mass  which  is  very  difficult  to  filter. 

1  A.  238, 183. 

2  A  few  of  them,  however,  such  as  Para  Red,  are  produced 
directly  on  the  fibre  ("  ice  colours  ").    The  fabric  is  first  soaked 
in  a  solution  of  the  diazotised  amine  (e.g.  ^.-nitraniline)  and 
then  passed   into  an   alkaline  solution  of   a  phenol,  usually 
/3-naphthol. 


25o      PREPARATION  OF  ORGANIC  COMPOUNDS 

In  order  to  avoid  using  an  unnecessarily  large  quantity  of 
salt  and  thus  getting  an  impure  product,  the  process  of 
salting-out  should  be  followed  by  "spotting"  the  solu- 
tion on  filter-paper  from  time  to  time.  The  appearance 
of  the  spot  will  show  how  far  the  salting-out  has  gone. 

The  aminoazo-compounds  are  formed  in  neutral 
or  weakly  acid  solution,  or  in  the  presence  of  acetic 
acid,  but  in  the  case  of  the  aminoazo-benzenes  the 
isomeric  diazoamino  -  compound  is  usually  formed 
(cf.  p.  239).  With  the  naphthylamines,  however,  the 
aminoazo-compound  is  the  sole  product.  The  coupling 
is  usually  brought  about  by  adding  the  diazo-solution 
to  a  solution  of  the  base  in  hydrochloric  acid,  and 
then  adding  sodium  acetate  until  no  more  mineral 
acid  is  present  (Congo  paper).  The  formation  of  the 
azo-compound  is  usually  complete  in  the  course  of 
an  hour,  during  which  time  the  solution  must  be 
kept  ice-cold  in  order  to  prevent  the  decomposition  of 
the  diazo-compound.  If  insoluble  it  can  be  filtered 
off  directly,  but  if  soluble  must  be  precipitated  as  in 
the  case  of  the  oxyazo-compounds  (vide  supra) . 

Experimental  details  for  the  preparation  of  a  number 
of  representative  azo-colours  will  be  found  in  "  The 
Synthetic  Dyestuffs,"  by  Cain  and  Thorpe.  The 
method  will  be  illustrated  here  by  three  examples. 

PREPARATION  OF  ORANGE  II.  Sulphanilic  acid 
(I7'3  §rm-)  is  dissolved  in  300  c.c.  of  water  containing  4^-5  grm. 
of  caustic  soda,  and  ice  added  until  the  temperature  falls 
below  5°.  The  solution  is  then  neutralised  with  hydrochloric 
acid,  another  30  c.c.  of  concentrated  hydrochloric  acid  added, 
and  the  solution  diazotised  with  7-2  grm.  of  sodium  nitrite  in 
about  50  c.c.  of  water.  The  nitrite  must  be  added  slowly, 
and  the  temperature  kept  below  5°.  When  all  the  nitrite 
has  been  run  in,  the  solution  should  show  a  faint  reaction  to 
starch  iodide  paper.  If  this  is  not  the  case  a  little  more 
nitrite  should  be  added.  The  diazo- chloride  separates  out  in 
fine  needles,  but  must  on  no  account  be  filtered  off  or  allowed 
to  dry,  as  it  is  very  explosive. 

/3-Naphthol  (14-4  grm.)  is  dissolved  by  heating  with  4-5  grm. 
of  caustic  soda  and  15  c.c.  of  water  and  then  pouring  the 
solution  into  1 50  c.c.  of  cold  water.  The  solution  thus  obtained 


THE  DIAZO-,   ETC.,  COMPOUNDS  251 

is  cooled  to  15°,  and  the  suspension  of  the  diazo-salt  obtained 
as  above  run  in  slowly  with  continual  stirring.  The  whole 
should  be  tested  from  time  to  time  to  make  certain  that 
sufficient  alkali  is  present.  After  standing  for  an  hour  most  of 
the  dye  will  have  separated  from  the  solution.  The  rest  is 
precipitated  by  the  addition  of  salt,  and  the  whole  filtered  off 
and  dried.  The  yield  is  34  grm. 

HO 


NaS03 


PREPARATION  OF  BENZOPURPURIN  48.1  Tolidine 
(2 1 '2  grm.)  is  dissolved  in  300  c.c.  of  hot  water  and  20  c.c.  of 
concentrated  hydrochloric  acid,  the  solution  cooled  to  5°, 
another  30  c.c.  of  concentrated  hydrochloric  acid  added,  and 
the  whole  diazotised  as  usual  with  a  solution  of  14.4  grm.  of 
sodium  nitrite.  The  solution  thus  obtained  is  poured  into  a 
suspension  of  54  grm.  of  finely  ground  sodium  naphthionate  in 
i oo  c.c.  of  cold  water,  and  the  whole  well  stirred.  At  the  end  of 
half  an  hour  the  addition  of  a  solution  of  3  5  grm.  of  anhydrous 
sodium  carbonate  is  commenced,  but  the  addition  is  made  so 
slowly  that  the  whole  of  the  carbonate  has  not  been  run  in 
until  twenty-four  to  thirty-six  hours  have  elapsed.  The 
solution  is  then  heated  to  80°,  and  the  dyestuff  salted-out. 
It  forms  a  brown  powder  which  dyes  cotton  red  from  an 
alkaline  bath. 

S03Na 


,CH 


NH2 
NH2 


CH3  \/\/ 

SO3Na 
Benzopurpurin  46 

1  Cain  and  Thorpe,  "  Synthetic  Dyes  tuffs  "  (1905),  p.  231 


252      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION    OF     I-PHENYL-3-METHYL-4-PHENYL- 

MeC— CHN  :  NPh 

AZO-5-PYRAZALONE,  *  NcO  Phenyl-methyl- 

N— NPh 

pyrazalone  (17-4  grm.)  is  dissolved  in  glacial  acetic  acid,  the 
solution  cooled  with  ice,  and  then  treated  slowly  with  diazo- 
benzene  chloride  solution  obtained  from  9-3  grm.  of  aniline. 
The  azo-compound  is  collected,  washed  with  water,  and  re- 
crystallised  from  glacial  acetic  acid.  It  forms  orange-red 
needles  with  a  blue  reflex,  which  melt  at  155°. 

Aminoazo-compounds  can  also  be  obtained  by  the 
intramolecular  rearrangement  of  the  diazoamino- 
compounds.  The  rearrangement  is  brought  about  by 
heating  with  the  primary  base  and  its  hydrochloride  : 

C6H5N=N.NH.C6H5    -*     C6H5N-N.C6H4NH2 

and  this  method  is  of  value  for  preparing  aminoazo- 
compounds  which  cannot  be  obtained  by  coupling, 
owing  to  the  formation  of  diazoamino-compounds. 
The  amino-group  takes  the  para-  position  to  the  azo- 
group  if  this  is  free.  If  the  para-  position  is  occupied, 
the  ortho-  position  is  taken,  but  the  reaction  does  not 
usually  proceed  smoothly. 

PREPARATION  OF  £.-AMINOAZOBENZENE  (ANILINE 
YELLOW)  (NH2C6H4N2C6H6).2  Ten  grammes  of  finely  ground 
diazoamino-benzene  and  5  grm.  of  aniline  hydrochloride  are 
well  mixed  with  25  grm.  of  aniline,  and  the  whole  heated  on 
the  water-bath  to  45°  for  one  hour  with  frequent  shaking. 
After  standing  over-night  the  whole  is  mixed  with  a  little 
water,  and  then  fairly  strong  hydrochloric  or  acetic  acid  added 
until  all  the  aniline  has  gone  into  solution,  care  being  taken  to 
prevent  any  considerable  rise  in  temperature.  After  cooling, 
the  precipitate  is  collected  by  filtration  and  washed  with  a 
little  cold,  very  dilute  hydrochloric  acid.  The  hydrochloride 
which  remains  on  the  filter  can,  if  desired,  be  recrystallised 
from  hot,  very  dilute  hydrochloric  acid.  In  order  to  obtain 
the  free  base,  the  hydrochloride  is  warmed  with  a  little  dilute 
ammonia,  filtered,  and  then  recrystallised  from  aqueous 

1  A.  238,  183.       2  B.  10    1309  ;  20,  372,  904  ;   Soc.  47,  923. 


THE  DIAZO-,  ETC.,  COMPOUNDS  253 

alcohol  containing  a  little  ammonia.  It  forms  orange-red 
prisms  which  melt  at  127°.  The  yield  is  about  70  per  cent. 

The  oxyazo-compounds  can  be  obtained  in  a  similar 
way  by  warming  the  diazoamino-compounds  with 
phenols  : 

Ar  .  NH  .  N  :  NAr  +  ArOH  =  ArN  :  N  .  ArOH  +  ArNH2. 

The  azoxy-compounds  are  also  rearranged  to  oxy- 
azo-compounds by  warming  with  concentrated  sulphuric 
acid.1 

From  a  theoretical  point  of  view  the  formation  of 
oxyazo-compounds  by  the  action  of  hydrazines  on 
quinones  is  of  interest  as  pointing  to  the  quinonoid 
structure  : 


0-C10H7=  ;OH2J 

1 
0=C10H7=N—  NHC6H5. 

With  benzoquinones  the  reaction  only  takes  place 
when  the  hydrazine  contains  negative  groups  in  the 
ortho-  or  para-  position.  Thus  phenylhydrazine  does 
not  give  an  azo-compound  with  benzoquinone,  but 
azo-compounds  are  obtained  when  [2]  or  [4]  mononitro- 
or  [2.4]  dinitro-phenylhydrazine  is  employed.  It  is 
curious  that  [2.4.6]  trinitro-phenylhydrazine  will  not 
give  an  azo-compound.  For  further  information  on 
this  subject  the  reader  is  referred  to  the  literature.2 

Finally,  it  may  be  pointed  out  that  nitroazo-com- 
pounds  can  be  reduced  to  aminoazo  -  compounds 
by  treatment  with  ammonium  sulphide,  the  azo- 
group  not  being  attacked  when  the  reduction  is  carried 
out  under  suitable  conditions.  This  method  is  useful 
for  preparing  the  disazo  -  colours  derived  from 
^.-phenylenediamine  (see  p.  241). 

1  B.  13,  525  ;   A.  215,  218. 

2  A.  340,  85  ;  357,  171  ;  360,  n  ;   B.  17,  3026  ;   28,  2415. 


254      PREPARATION  OF  ORGANIC  COMPOUNDS 

V.  THE  AZOXY-COMPOUNDS 

The  azoxy-compounds  contain  the  group 

/°\ 

R— N— N  — R 

and  may  be  regarded  as  the  first  oxidation  products 
of  the  azo-compounds.  They  are  invariably  obtained 
by  the  alkaline  reduction  of  the  corresponding  nitro- 
or  nitroso-compounds,  the  reduction  being  effected  by 
means  of  alcoholic  soda  or  potash,  sodium  amalgam  and 
alcohol,  zinc  dust  and  alcoholic  ammonia,  or  by 
alkaline  potassium  arsenite.  The  reduction  can  also 
be  carried  out  by  the  electrolysis  of  the  nitro-compound 
in  dilute  caustic  soda.1  n 

/    \ 
PREPARATION  OF  AZOXYBENZENE  (C6H5N  =  N.C6H6). 

(a)  2  Twenty  grammes  of  sodium  are  slowly  added  to  200  grm. 
of  methyl  alcohol,  contained  in  a  flask  fitted  with  a  reflux 
condenser.  When  the  sodium  has  dissolved,  30  grm.  of  nitro- 
benzene are  added,  and  the  whole  boiled  on  the  water-bath  for 
five  hours.  The  alcohol  is  then  distilled  off,  and  the  residue 
poured  into  cold  water  and  thoroughly  stirred.  After  the  oil 
has  solidified  it  is  well  washed  with  water,  dried  by  pressing 
between  filter-paper,  and  then  recrystallised  from  ligroin, 
in  which  it  is  easily  soluble.  It  forms  yellow  needles  which 
melt  at  36°.  The  yield  is  about  90  per  cent. 

(b)  3  Twenty-five  grammes  of  nitrobenzene  are  boiled  under 
a  reflux  condenser  for  eight  hours  with  30  grm.  of  arsenic 
trioxide,  40  grm.  of  caustic  soda,  and  400  c.c.  of  water.  After 
cooling,  the  oil  is  collected,  washed  several  times  with  water, 
made  slightly  acid  with  dilute  sulphuric  or  hydrochloric  acid, 
and  then  distilled  in  steam.  A  little  unchanged  nitrobenzene 
passes  over  first,  and  then  pure  azoxy benzene.  The  yield  is 
60-70  per  cent. 

1  B.  33,  2332. 

2  J-  pr.  [i]  36,  98  ;   B.  15,  865. 

3  J-  pr.  [2]  50,  564  ;  D.R.P.  77,563- 


THE  DIAZO-,  ETC.,  COMPOUNDS  255 

VI.  THE    HYDRAZO-COMPOUNDS 

The  hydrazo  -  compounds  contain  the  group 
R.NH.NH.R,  and  are  invariably  obtained  by  the 
moderated  reduction  of  the  nitro-,  nitroso-,  or  azo- 
compounds.  In  order  to  avoid  the  intramolecular 
rearrangement  of  the  hydrazo-compound  to  a  benzidine 
derivative  (see  p.  217),  the  reduction  must  be  carried 
out  in  neutral  or  alkaline  solution. 

The  nitro-compounds  are  best  reduced  with  zinc 
dust  and  caustic  soda  in  aqueous  alcoholic  solution. 
Instead  of  zinc  dust,  the  cheaper  lead  powder  x  can  be 
used.  The  'electrolytic  method  also  gives  satisfactory 
yields.2 

The  azo-compounds  are  best  reduced  with  zinc  dust 
and  alcohol,  alcoholic  ammonium  sulphide,  iron  powder 
and  caustic  soda,  and  sodium  or  aluminium  amalgam 
and  alcohol. 

PREPARATION  OF  HYDRAZOBENZENE  (C6H5NH. 
NHC6H5).  (a)  3  Fifty  grammes  of  nitrobenzene  and  25  grm. 
of  alcohol  are  heated  to  boiling  under  a  reflux  condenser, 
and  80  grm.  of  zinc  dust  added.  To  the  gently  boiling  mixture 
a  solution  of  3  grm.  of  caustic  soda  in  50  c.c.  of  90  per  cent. 
alcohol  is  slowly  added  during  two  to  three  hours.  After 
boiling  for  a  short  time  the  product  should  be  of  a  clear  grey 
colour.  Should  this  not  be  the  case,  a  little  water  and  a  little 
more  zinc  dust  must  be  added,  and  the  boiling  continued. 
When  the  reduction  is  complete  the  whole  is  diluted  with 
water,  the  alcohol  driven  off  in  a  current  of  steam,  and  the 
solid  residue  well  washed  on  a  sieve.  If  a  sieve  of  suitable 
mesh  is  used,  the  excess  of  zinc  dust,  &c.,  is  readily  washed 
away  from  the  crystalline  hydrazobenzene,  the  latter  remaining 
in  an  almost  pure  condition.  The  crude  product  can  also  be 
extracted  with  alcohol  in  a  Soxhlet  apparatus,  or  it  can  be 
suspended  in  a  large  volume  of  ice-water,  and  then  treated  very 
carefully  with  hydrochloric  acid.  The  latter  method,  however, 
is  very  apt  to  bring  about  the  benzidine  rearrangement 
(p.  217).  It  forms  colourless  plates  which  melt  at  125°.  The 
yield  is  about  90  per  cent. 

i  D.R.P.  81,129.  2  Z-  El.  Ch.  5,  108. 

3  Schultz,  "  Chemie  des  Steinkohlenteers  "  (1901),  vol.  i,  94. 


256      PREPARATION  OF  ORGANIC  COMPOUNDS 

(b) l  Azobenzene  is  dissolved  in  6  parts  of  alcohol,  a  little 
water  added,  and  the  whole  warmed  on  the  water-bath  with 
aluminium  amalgam  until  colourless.  It  is  then  filtered  hot, 
and  the  residue  extracted  with  alcohol  in  an  extraction 
apparatus.  The  aluminium  amalgam  is  prepared  as  follows. 
Aluminium  foil  is  treated  with  cold  10  per  cent,  caustic  soda 
until  a  brisk  evolution  of  hydrogen  sets  in.  The  caustic  soda 
solution  is  then  poured  off,  the  foil  washed  three  times  with 
cold  water,  covered  with  water,  and  a  little  i  per  cent,  mercuric 
chloride  solution  added.  After  a  few  seconds  the  solution  is 
poured  off,  the  foil  well  washed,  and  the  whole  process 
repeated . 

VII.    THE  HYDRAZINES 

The  hydrazo-compounds  considered  above  are  to  be 
regarded  as  the  symmetrical  di-substituted  derivatives 
of  hydrazine. 

The  hydrazines  are  the  mono-substituted  and  unsym- 
metrical  di-substituted  derivatives,  and  have  the 
general  formula  RR'N.NH2,  where  R  is  alkyl  or  aryl 
and  R/  alkyl,  aryl,  or  hydrogen.  Only  the  mono- 
substituted  products,  R.NH.NH2,  will  be  con- 
sidered. 

The  aliphatic  members,  with  the  exception  of  semi- 
carbazide,  NH2.CO.NH.NH2  (obtained  by  heating 
urea  with  hydrazine  hydrate  to  ioo°),2  are  of  no 
importance.  They  are  readily  obtained  by  acting  on 
the  alkylene  oxides  with  hydrazine  hydrate,  ethylene 
oxide  giving  two  compounds  : 

CH2X  CH2.NH.NH2  CH2.NH.NH2 

No   —     i  ->      i 


CH9 


CH2OH  CH2.NH.NH2 

Both  these  are  viscous  oils,  but  form  crystalline  con- 
densation products  with  formaldehyde,  e.g.  CH2OH. 
CH2NHN :  CH2. 

The  aromatic  derivatives  are  of  considerable  import- 
ance and  are  universally  obtained  by  the  reduction  of 
the  diazo-compounds.  A  large  number  of  methods 

1  J.  pr.  [2]  52,  141-  2  J-  pr.  [2]  52,  465. 


THE  DIAZO-,  ETC.,  COMPOUNDS  257 

have  been  proposed  for  effecting  the  reduction,  of  which 
the  following  may  be  mentioned :  Sulphurous  acid 
(sulphites  and  bisulphites),  zinc  dust  and  alkali,  zinc 
dust  and  acetic  or  hydrochloric  acid,  sodium  amalgam, 
sodium  stannite,  and  stannous  chloride  and  hydro- 
chloric acid.  Of  these  sulphurous  acid,  stannous 
chloride,  and  zinc  dust  and  acetic  acid  are  the  ones 
most  frequently  used. 

PREPARATION  OF  PHENYLHYDRAZINE  (C6H5NHNH2)  .1 
Twenty  grammes  of  aniline  are  dissolved  in  about  180  c.c.  of 
concentrated  hydrochloric  acid,  the  solution  cooled  below  o° 
in  a  freezing  mixture,  and  then  diazotised  in  the  usual  way 
until  a  permanent  reaction  is  obtained  with  starch -iodide  paper 
(20  grm.  sodium  nitrite).  Without  removing  the  solution 
from  the  freezing  mixture  a  cold  solution  of  120  grm.  of 
stannous  chloride  in  about  100  c.c.  of  concentrated  hydro- 
chloric acid  is  added.  After  standing  for  an  hour  the  phenyl- 
hydrazine  hydrochloride  is  filtered  off.  In  order  to  obtain  the 
free  base  it  is  well  shaken  or  ground  up  with  excess  of  caustic 
soda  solution,  the  oil  which  separates  extracted  with  ether, 
and  the  ethereal  solution  dried  with  potassium  carbonate. 
The  ether  is  then  distilled  off  and  the  residual  oil  fractionated 
in  vacuo.  It  forms  an  almost  colourless  oil  which  soon  assumes 
a  red  colour.  B.P.  241°  at  760  mm.,  with  slight  decom- 
position, and  at  120°  at  12  mm.  without  decomposition. 
M.P.  23°.  As  phenylhydrazine  is  poisonous  care  should  be 
taken  not  to  inhale  its  vapour  or  to  allow  the  liquid  to  come 
in  contact  with  the  skin. 

*  B.  16,  2976  ;   17,  572. 


CHAPTER  XII 

SULPHINIC  AND  SULPHONIC  ACIDS 
SULPHINIC  ACIDS,  R.S02H 

THE  sulphinic  acids  are  of  but  little  importance,  and 
only  require  mention  as  the  members  of  the  aromatic 
series  are  often  readily  obtained  from  the  corresponding 
diazo-compounds  by  the  action  of  sulphurous  acid  and 
copper  powder,  and  sometimes  form  a  convenient  source 
of  sulphonic  acids,  into  which  they  readily  pass  by 
oxidation  with  permanganate. 

In  replacing  the  diazo-group  by  the  sulphinic  acid 
group  very  careful  cooling  is  necessary.  The  amine  is 
diazotised  in  the  usual  way  with  sulphuric  acid  and 
sodium  nitrite,  and  the  solution  then  saturated  with 
sulphur  dioxide x  until  every  100  c.c.  of  liquid  has 
taken  up  at  least  15  grm.  of  the  gas.  The  solution 
should  remain  clear.  Without  interrupting  the  stream 
of  gas,  and  with  continual  careful  cooling,  copper  powder 
(see  p.  75)  is  added  little  by  little  until  on  interrupt- 
ing the  stream  of  SO2  for  a  minute  it  sinks  to  the  bottom 
of  the  vessel.  If  the  sulphinic  acid  is  insoluble  in  water 
it  is  filtered  off,  dissolved  in  carbonate  solution,  filtered 
free  from  copper,  and  then  reprecipitated  with  acid. 
Otherwise  the  solution  must  be  extracted  with  ether, 
chloroform,  or  other  solvent,  the  extract  shaken  up 
with  sodium  carbonate  solution,  the  aqueous  layer 
separated  and  acidified,  and  then  re-extracted  with  a 

1  Liquid  sulphur  dioxide  can  be  bought  in  glass  siphons, 
and  these  form  the  most  convenient  source  of  the  gas.  Other- 
wise it  can  be  evolved  by  dropping  concentrated  sulphuric 
acid  into  technical,  40  per  cent,  bisulphite  solution. 

258 


SULPHINIC  AND  SULPHONIC  ACIDS  259 

suitable  solvent.  On  removing  the  solvent  the  sulphinic 
acid  is  left  behind.  As  some  sulphinic  acids  are  very 
sensitive  to  heat  it  is  best  either  to  let  the  solvent 
evaporate  spontaneously  at  the  ordinary  temperature, 
or  to  distil  off  under  reduced  pressure  from  as  cool  a 
water-bath  as  possible. 

The  acids  can  also  be  quantitatively  precipitated  as 
their  ferric  salts  by  adding  ferric  chloride  to  the  strongly 
acid  solution.1 

Instead  of  copper  powder,  cuprous  oxide  may  be  used2 
or  excess  of  sodium  bisulphite  may  be  added,  then 
an  alcoholic  solution  of  sulphurous  acid,  and  finally  a 
small  quantity  of  copper  sulphate.3 

PREPARATION  OF  NAPHTHALENE- I.4-SULPHOSUL- 
PHINIC  ACID.4  Sixty  grammes  of  sodium  naphthionate  (sodium 
naphthylamine  sulphonate  [1.4])  are  diazotised  in  the  usual 
way  (see  p.  238)  with  250  c.c.  of  13  per  cent,  hydrochloric 
acid  and  200  c.c.  of  6  per  cent,  sodium  nitrite  solution.  The 
diazo-salt  is  insoluble  and  separates  out,  but  must  on  no  account 
be  filtered  off  as  it  is  extremely  explosive.  The  liquid  is 
then  saturated  with  sulphur  dioxide  (at  least  50  grm.  of  the 
gas  must  be  taken  up),  the  temperature  being  kept  below  o°. 
Copper  powder  (see  p.  75)  is  then  added  little  by  little  until 
no  more  nitrogen  is  evolved,  a  slow  stream  of  sulphur  dioxide 
being  passed  through  the  liquid  the  whole  time.  After 
filtration  the  liquid  is  saturated  with  common  salt,  when  the 
acid  sodium  salt  of  the  sulphosulphinic  acid  is  precipitated 
in  almost  quantitative  yield.  After  recrystallisation  from 
water  it  forms  colourless  leaflets. 

On  dissolving  the  sodium  salt  in  water  and  then  saturating 
the  solution  with  gaseous  hydrochloric  acid,  the  free  acid  is 
precipitated  in  glittering  needles. 

For  details  of  the  preparation  of  other  sulphinic  acids 
by  this  method  the  reader  is  referred  to  Gattermann's  original 


paper.5 


i   Soc.  95,  342.  2  D.R.P.  100,702. 

3  D.R.P.  130,119.  4  B.  32,  1146. 

5  B.  32,  1136  et  seq.  ;    Soc.  95,  342. 


260      PREPARATION  OF  ORGANIC  COMPOUNDS 

SULPHONIC  ACIDS,  RS03H 

AROMATIC  SERIES.  As  the  aromatic  sulphonic 
acids  are  infinitely  more  important  than  the  aliphatic, 
they  alone  will  be  discussed.  The  methods  for  introduc- 
ing the  sulphonic  acid  group  are  two  in  number,  viz.  : 

(i)  DIRECT  SULPHONATION.  This  is  by  far  the 
most  important  method  and  consists  in  heating  the 
aromatic  compound  with  sulphuric  acid.  Either 
ordinary  vitriol  is  used,  in  which  case  phosphoric 
anhydride  or  anhydrous  potassium  sulphate  may  be 
added  to  remove  the  water  formed  during  the 
reaction  : 

RH  +  H2S04  =  R.S03H  +  H20 

or  the  fuming  acid  (oleum)  is  employed.  Oleums  of 
certain  concentrations  are  apt  to  go  solid  when  standing 
in  the  laboratory,  and  in  this  case  must  be  melted 
before  use.  To  do  this  the  stopper  is  removed,  and 
the  mouth  of  the  bottle  closed  by  laying  a  watch-glass 
over  it.  The  bottle  is  then  placed  on  a  layer  of  dry 
sand  about  3  in.  deep  in  a  bucket,  and  about  half 
buried  in  the  same  substance.  The  bucket  is  then 
heated  with  a  small  flame  until  the  acid  is  melted. 
Under  no  circumstances  should  the  bottle  be  heated  in 
a  water-bath,  as,  should  the  bottle  crack,  the  acid  coming 
in  contact  with  the  hot  water  may  give  rise  to  a  serious 
accident.  Sulphonation  is  also  sometimes  brought 
about  by  means  of  chlorsulphonic  acid  (cf.  p.  73). 

In  order  to  isolate  the  sulphonic  acid  from  the  sul- 
phonation  mixture  the  latter  is  poured  into  water, 
and  the  sulphonic  acid  either  salted  out  by  saturating 
the  solution  with  common  salt  or  potassium  chloride,1 
or  the  solution  is  neutralised  with  chalk,  or  barium  or 
lead  carbonate.  The  precipitated  sulphate  is  then 
removed  by  nitration  while  hot  and  well  washed  with 

1  The  acid  comes  out  as  the  sodium  or  potassium  salt, 
usually  contaminated  with  sodium  or  potassium  chloride.  It 
can  often  be  purified  by  alcohol,  in  which  NaCl  and  KC1  are 
insoluble. 


SULPHINIC  AND  SULPHONIC  ACIDS  261 

boiling  water.  The  filtrate,  which  contains  the 
calcium,  barium,  or  lead  salt  of  the  sulphonic  acid, 
is  then  concentrated  until  crystallisation  takes  place. 
To  obtain  the  sodium  salt  the  boiling  solution  of  the 
calcium,  &c.,  salt  is  treated  with  sodium  carbonate 
until  no  more  precipitation  takes  place.  The  precipi- 
tated carbonate  is  then  removed  by  filtration,  and  the 
filtrate  concentrated. 

To  obtain  the  free  acid  either  the  calcium,  barium,  or 
lead  salt  is  treated  with  exactly  one  equivalent  of 
sulphuric  acid  and  the  filtrate  concentrated,  or,  what  is 
better,  the  lead  salt  is  decomposed  by  sulphuretted 
hydrogen  and  the  precipitated  lead  sulphide  removed 
by  filtration. 

The  temperature  at  which  the  sulphonation  is  carried 
out  sometimes  affects  the  position  of  the  entering 
group.  Thus  naphthalene  sulphonated  below  80° 
gives  the  a-sulphonic  acid,  whereas  above  80°  the 
/3-acid  is  exclusively  formed.  A  similar  directing 
influence  is  exerted  by  traces  of  mercury  salts  during 
the  sulphonation  of  anthraquinone.  Thus  under 
ordinary  conditions  the  sulphonic  group  enters  the 
/3-  position,  but  in  the  presence  of  mercuric  sulphate 
(o-i  per  cent.)  the  a-acid  is  exclusively  formed. 

According  to  D.R.P.  214,516,  small  quantities  of 
vanadium  salts  have  a  beneficial  effect  on  the  course 
of  the  reaction.  A  similar  influence  is  exerted  by 
infusorial  earth. 

A  variation  of  the  above  method  of  sulphonation, 
often  used  technically  for  preparing  amino-sulphonic 
acids,  consists  in  roasting  the  sulphate  of  the  base. 
The  sulphonic  group  then  enters  the  p.-  position  to  the 
amino-group. 

NH2H2SO4  NH2 


S03H 
Naphthionic  acid 


262      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  CALCIUM  BENZENE  SULPHONATE 
(PhSO3)2Ca.1  Fifty  grammes  of  benzene  are  added  to  300  grm . 
of  concentrated  sulphuric  acid  (66°  Be.)  Ignited  infusorial 
earth  (Kieselguhr)  is  then  added  until  the  whole  forms  a 
stiff  meal.  The  mixture  is  allowed  to  stand  for  twenty-four 
hours  at  the  ordinary  temperature,  after  which  it  is  mixed 
with  2000  c.c.  of  water.  The  boiling  solution  is  then  neutralised 
with  chalk,  filtered  from  calcium  sulphate,  and  the  precipitate 
well  washed  with  boiling  water.  The  united  filtrates  are  then 
concentrated  until  crystallisation  sets  in.  On  cooling,  the 
calcium  salt  separates  out  and  may  be  further  purified  by 
recrystallisation  from  a  little  boiling  water  with  addition 
of  animal  charcoal.  If  a  good  quality  of  guhr  is  used,  the 
benzene  is  completely  converted  into  its  monosulphonic  acid. 

PREPARATION    OF    SODIUM    a-NAPHTHALENE    SUL- 
SO,Na 


PHONATE,2 


Forty    grammes    of    finely    pow- 


\/\/ 

dered  naphthalene  are  added  to  30  grm,  of  concentrated 
sulphuric  acid  (monohydrate  is  best)  and  the  whole  heated 
for  eight  to  ten  hours  to  a  temperature  of  75°-8o°.  This 
latter  temperature  must  on  no  account  be  exceeded  (see 
p.  261).  The  mixture  is  then  poured  into  350  c.c.  of  hot  water, 
and,  after  cooling,  excess  of  naphthalene  removed  by  filtration. 
The  filtrate  is  then  heated  to  boiling  and  neutralised  with 
lead  carbonate.  The  precipitated  lead  sulphate  is  filtered  off, 
washed  with  boiling  water,  and  the  filtrate  concentrated 
until  crystals  begin  to  form.  The  first  crystals  that  separate 
are  contaminated  with  the  lead  salt  of  the  /3-acid  and  are 
therefore  removed  by  filtering  the  hot  liquid,  and  are  rejected. 
On  further  concentrating  the  filtrate  and  then  cooling, 
the  more  soluble  a-salt  is  obtained  mixed  with  a  little  of  the 
/3-salt,  and  some  lead  sulphate.  It  is  therefore  dissolved  in 
10-12  parts  of  boiling  alcohol  and  filtered  from  the  insoluble 
/3-salt  and  lead  sulphate.  On  cooling,  the  pure  salt  separates 
out  in  colourless  leaflets  containing  three  molecules  of  water. 
To  convert  it  into  the  sodium  salt  it  is  dissolved  in  boiling 
water  and  sodium  carbonate  solution  added  until  no  further 
precipitation  takes  place.  The  lead  carbonate  is  then  removed 

i  D.R.P.  71,556.  2  B.  3,  196. 


SULPHINIC  AND  SULPHONIC  ACIDS 


263 


by  filtration  and  the  filtrate  concentrated  until  crystallisation 
sets  in. 

PREPARATION    OF    SODIUM    /3-NAPHTHALENE     SUL- 


SO3Na 
PHONATE,1  Fifty  grammes  of  naphthalene  and 

\/\/ 

40  grm.  of  concentrated  sulphuric  acid  are  heated  to 
1 60°  for  eight  hours.  The  resulting  mixture  is  poured  into 
about  400  c.c.  of  water,  and  after  cooling  filtered  from  un- 
changed naphthalene.  The  filtrate  is  heated  to  boiling, 
neutralised  with  chalk,  and  the  filtrate  and  washings  from 
the  calcium  sulphate  concentrated  until  crystallisation  sets 
in.  The  calcium  salt  thus  obtained  is  dissolved  in  boiling 
water  and  treated  with  sodium  carbonate  until  no  more  preci- 
pitation takes  place.  The  nitrate  is  then  concentrated  until 
the  sodium  salt  crystallises  out.  This  is  finally  purified  by 
recrystallisation  from  a  little  boiling  water  containing  animal 
charcoal. 

PREPARATION     OF     POTASSIUM      ANTHRAQUINONE 

S03K 


CO 


a-SULPHONATE,2 


Fifty     grammes     of 


anthraquinone  are  carefully  ground  up  with  0-5  grm.  mercuric 
sulphate,  and  the  whole  added  to  60  grm.  of  20  per  cent,  oleum 
contained  in  a  flask  or  cast-iron  or  lead  pot.  The  whole  is 
then  heated  in  an  oil-bath  for  three-quarters  of  an  hour  to  a 
temperature  of  150°,  and  must  be  mechanically  stirred  the 
whole  time.  The  melt  is  poured  into  500  c.c.  of  boiling  water, 
the  whole  boiled  and  then  filtered  while  hot  from  unchanged 
anthraquinone.  The  precipitate  is  well  washed  with  boiling 
water,  and  the  united  filtrates  heated  to  90°,  at  which  tempera- 
ture 50  c.c.  of  a  cold  saturated  solution  of  potassium  chloride 
are  added.  The  slightly  soluble  potassium  salt  begins  to 
separate  almost  at  once  as  pale  yellow  glittering  leaflets,  which 
after  standing  over-night  at  the  ordinary  temperature  are 
filtered  off  from  the  dark-coloured  liquid  and  washed  with  cold 

1  B.  3,  196. 

2  D.R.P.  149,801  ;  B.  36,  4197  ;  37,  67. 


264      PREPARATION  OF  ORGANIC  COMPOUNDS 

water.     Yield  about   75   per  cent.,  allowing  for  the   anthra- 
quinone  recovered  unchanged. 

On  sulphonating  anthraquinone  without  the  addition 
of  mercury  salts,  the  /3-acid  is  exclusively  formed. 


PREPARATION   OF  SULPHANILIC   ACID, 

Acid  aniline  sulphate,  C6H5NH2  .  H2SO4,  is  first  prepared  by 
stirring  100  grm.  of  aniline  into  60  c.c.  of  concentrated 
sulphuric  acid  in  a  shallow  basin.  The  whole  is  then  heated 
in  an  oven  so  that  at  the  end  of  four  hours  the  tempera- 
ture has  reached  205°.  This  temperature  is  maintained  for 
another  six  hours,  and  the  melt  is  then  broken  up  and  dis- 
solved in  hot  water,  sufficient  caustic  soda  being  added  to 
give  an  alkaline  reaction  (about  40  grm.).  The  solution  is 
then  boiled  for  a  few  minutes  with  animal  charcoal  and 
filtered  hot.  On  treating  the  filtrate  with  hydrochloric  acid 
until  acid  to  Congo  paper,  the  sulphanilic  acid  crystallises  out, 
and,  after  standing  over-night,  is  filtered  off  and  dried  at  100°. 
It  forms  large  colourless  plates.  Yield  about  150  grm. 

Treatment  with  sulphites  or  bisulphites  often  causes 
the  entrance  of  the  sulphonic  acid  group,  especially 
in  compounds  of  a  quinonoid  character.  Nitro-groups, 
if  present,  are  often  simultaneously  reduced  to  amino- 
groups,  or  may  themselves  he  replaced  l  by  the  sul- 
phonic group. 

PREPARATION  OF  w.-NITRANILINE  SULPHONIC  ACID 

(C6H3  [  i  ]NH2  [3  ]NO2  [4]SO3H)  .  2  Thirty-three  grammes  of 
m.-dinitrobenzene  are  added  in  small  quantities  to  100  grm. 
of  neutral  sodium  sulphite  dissolved  in  400-500  c.c.  of  warm 
water,  the  whole  being  vigorously  stirred.  As  soon  as  the 
dinitrobenzene  melts,  a  vigorous  reaction  sets  in,  and  after 
a  short  time  a  clear  solution  is  obtained.  The  nitraniline 
sulphonic  acid  is  precipitated  as  yellow  needles  by  adding 
about  50  c.c.  of  concentrated  hydrochloric  acid. 

PREPARATION  OF  p.-PHENYLENEDIAMINE  SUL- 
PHONIC ACID  (C6H3[i.4](NH2)2[2]S03H).3  Thirty-two 

1  B.  15,  597. 

2  D.R.P.  86,097  J    B.  29,  2448. 

3  D.R.P.  64,908. 


SULPHINIC  AND  SULPHONIC  ACIDS  265 

grammes  of  quinone  dichlorimide  are  mixed  to  a  paste 
with  a  little  water  and  then  added  to  200  c.c.  of  a  50  per  cent. 
solution  of  sodium  bisulphite.  After  standing  for  a  short  time 
at  the  ordinary  temperature  the  reaction  sets  in  with  evolution 
of  sulphur  dioxide,  but  it  must  be  rendered  complete  by  warm- 
ing on  the  water -bath  for  a  short  time.  After  cooling,  the 
white  precipitate  is  collected  and  recrystallised  from  hot  water. 
The  acid  forms  colourless  needles  containing  two  molecules  of 
.  water  of  crystallisation. 

Instead  of  starting  with  the  ready  prepared  dichlorimide, 
C1N  :  C6H4  :  NCI,  the  di-imide,  NH  :  C6H4 :  NH,  can  be  pre- 
pared by  the  oxidation  of  ^.-phenylenediamine,  and  the 
solution  thus  obtained  treated  directly  (without  isolating 
the  di-imide)  with  sodium  sulphite.  To  carry  out  the  pre- 
paration by  this  method  30  grm.  of  ^.-phenylenediamine 
hydrochloride  are  added  to  240  c.c.  of  water  and  120  c.c.  of 
acetic  acid  of  about  40  per  cent,  strength.  The  mixture  is 
cooled  with  ice,  and  then  i6£  grm.  of  sodium  or  potassium 
bichromate  dissolved  in  180  c.c.  of  water  added.  To  the  green 
solution  thus  obtained,  70  grm.  of  crystallised  sodium  sulphite 
dissolved  in  180  c.c.  of  water  are  added,  whereupon  the  solution 
becomes  colourless  and  the  phenylenediamine  sulphonic  acid 
is  precipitated  as  a  crystalline  mass.  This  is  recrystallised  as 
before.  As  the  di-imide  is  a  very  unstable  substance  it  is 
better  to  add  the  sulphite  before  adding  the  bichromate. 
Yield  about  50  per  cent. 

NH2  NH 

/\ 


-S03H 
H2S03     = 


NH  NH2 


266     PREPARATION  OF  ORGANIC  COMPOUNDS 

(ii)  OXIDATION   OF   SULPHINIC   ACIDS.     As  the 

sulphinic  acids  are  readily  obtained  from  the  corre- 
sponding amines  by  means  of  Gattermann's  diazo- 
reaction,  this  method  affords  a  ready  means  of  obtaining 
sulphonic  acids,  such  as  naphthalene-i.4-disulphonic 
acid,  which  cannot  be  obtained  by  direct  sulphonation. 
The  oxidation  is  brought  about  either  by  potassium 
permanganate  in  alkaline  solution,1  or  the  ferric  salt 
of  the  sulphinic  acid  is  treated  with  ammonia  and 
sodium  hypochlorite,2  and  the  resulting  sulphonamide, 
R.S02NH2,  decomposed  by  boiling  with  dilute  alkali. 

PREPARATION  OF  NAPHTHALENE- M-DISULPHONIC 
ACID.3  Thirty  grammes  of  the  acid  sodium  salt  of  naphthalene 
sulphosulphinic  acid  described  on  p.  259  are  dissolved  in  a  little 
hot  water  (about  200  c.c.)  containing  14  grm.  of  caustic  potash. 
Thirty-three  grammes  of  potassium  permanganate  are  then 
added,  and  the  whole  heated  on  the  water-bath  for  an  hour. 
Excess  of  permanganate  is  then  removed  by  adding  a  small 
quantity  of  alcohol,  and  the  precipitated  manganese  dioxide 
removed  by  filtering  the  hot  liquid.  On  saturating  the  filtrate 
with  common  salt,  the  sodium  salt  of  the  disulphonic  acid  is 
precipitated  in  excellent  yield. 

PREPARATION  OF  BENZENE  SULPHINIC  AND  SUL- 
PHONIC ACIDS.4  Aniline  is  dissolved  in  dilute  sulphuric 
acid  (about  six  molecules)  and  diazotised  in  the  usual  way. 
The  diazo-solution  is  then  almost  saturated  with  sulphur 
dioxide,  the  temperature  being  kept  below  o°,  and,  without 
interrupting  the  stream  of  the  gas,  copper  powder  is  slowly 
added  until  no  more  nitrogen  is  evolved.  The  whole  is  then 
filtered  and  the  copper  well  washed  with  cold  dilute  ammonia. 
The  united  filtrates,  which  must  still  contain  an  excess  of  free 
sulphuric  acid,  are  treated  with  concentrated  ferric  chloride 
solution  until  no  more  precipitation  takes  place.  Ferric 
benzene  sulphinate  separates  in  quantitative  yield,  and  is  best 
converted  into  the  free  acid  by  shaking  with  a  slight  excess  of 
dilute  aqueous  ammonia.  On  adding  cold  concentrated 
hydrochloric  acid  to  the  filtrate,  the  free  acid  separates  out. 
M.P.  85°. 

i  B.  32,  1156.  2  Soc.  95,  342. 

3  B.  32,  1156.  4  Soc.  95,  342. 


SULPHINIC  AND  SULPHONIC  ACIDS  267 

In  order  to  obtain  the  sulphonic  acid,  18  grm.  of  iron  salt 
are  shaken  up  with  25  c.c.  of  concentrated  ammonia  and 
2 -5  grm.  of  ammonium  chloride.  A  slight  excess  of  sodium 
hypochlorite  is  added,  and  the  whole  allowed  to  stand  for  one 
hour.  It  is  then  made  acid  with  hydrochloric  acid  (use  Congo 
paper),  when  the  ferric  hydroxide  passes  into  solution,  leaving 
a  residue  of  benzene  sulphonamide,  C6H5SO2NH2.  This  can 
be  converted  into  the  acid  by  boiling  with  a  slight  excess  dilute 
caustic  soda  until  no  more  ammonia  is  evolved.  The  sodium 
salt  is  then  isolated  by  concentrating  the  solution. 


CHAPTER  XIII 
MISCELLANEOUS  TYPES 

THE  PYRAZOLONES 

THE  most  important  pyrazolones  are  the  5-pyrazolones 
which  contain  the  group 

4 


3  —  C          CO  5 

II  I 

N N 

2  I 

and  are  obtained  by  the  action  of  hydrazines  on 
/3-diketonic  compounds.  The  most  important  member 
of  the  series  is  i-phenyl-3-methyl-5-pyrazolonc.  * 

PREPARATION  OF  i  -  PHENYL  -  3  -  METHYL  -  5  -  PYRA- 
ZOLONE.1  Ten  grammes  of  phenyl  hydrazine  are  added  to 
1 2 -5  grin,  of  acetoacetic  ester,  and  the  whole  well  shaken. 
Considerable  heat  is  evolved,  and  when  the  reaction  is  over,  the 
oily  product  is  separated  from  the  water  formed  during  the 
reaction,  and  heated  on  the  water-bath  until  a  sample  poured 
into  ether  becomes  quite  solid  (about  two  hours).  The  whole 
is  then  poured  while  still  hot  into  ether,  the  white  precipitate 
collected,  well  washed  with  ether,  and  then  dried.  If  desired 
it  may  be  crystallised  from  hot  methyl  alcohol.  Colourless 
prisms  melting  at  127°.  The  yield  is  almost  quantitative. 

The  preparation  can  also  be  carried  out  by  heating  the  above 
quantities  of  phenyl  hydrazine  and  acetoacetic  ester  on  the 
water-bath  with  20  grm.  of  glacial  acetic  acid  until  a  sample 
when  poured  into  its  own  volume  of  ether  gives  a  hard  crystal- 

1  A.  238,  147  ;  B.  16,  2597  ;  D.R.P.  26,429. 
268 


MISCELLANEOUS  TYPES  269 

line  precipitate  (about  two  hours).     The  whole  is  then  poured 
into  100  c.c.  of  ether  and  the  pyrazolone  collected. 

CH3 .  C .  CH2 .  CO .  OC2H5  /         \ 

||  CH3.C  COiOEt! 

foi  -     ||     11:    1 

!  H2|N.NH.C6H5  ft NC6H5 


CH3.C  CO 

II  I 

N NC6H5 

The  above  compound  is  of  technical  importance,  as 
on  methylation  with  methyl  iodide  in  alcoholic  solution 
it  gives  antipyrine  : 

/CH\ 

CH3C  CO 

I  I 

CH3N-    — NC6H6 

used  in  medicine  as  an  antipyretic,  and  is  also  the 
mother-substance  of  some  azo-dyes. 


,/NH\/\ 


THE  ACRIDONES 

The  acridones  have  the  structure 


and  are  obtained  from  the  N-phenyl  anthranilic  acids 
(p.  227)  by  heating  with  dehydrating  agents,  such  as 
concentrated  sulphuric  acid  (at  9O°-ioo°)  or  anhydrous 
zinc  chloride. 

PREPARATION  OF  ACRIDONE.1     Ten  grammes  of  phenyl 
anthranilic  acid  are  dissolved  in  70-100  c.c.  of  concentrated 

i  B.  25,  1734. 


270      PREPARATION  OF  ORGANIC  COMPOUNDS 

sulphuric  acid,  and  the  whole  heated  on  the  water-bath  for 
from  two  to  three  hours.  After  cooling,  the  melt  is  poured  on 
to  crushed  ice  and  the  precipitate  collected,  well  washed  with 
caustic  soda  and  then  with  water,  and  finally  recrystallised 
from  boiling  alcohol.  It  forms  colourless  microscopic  needles 
which  exhibit  an  intense  violet  fluorescence  and  melt  at 
about  350°. 

THE  XANTHONES 


The  structure 


-\/°\/\ 


\/\co/\/ 


is   characteristic  of 


the  xanthones.  They  can  be  obtained  by  loss  of 
water  (cone.  H2SO4  at  100°  or  fused  ZnCl2)  from  the 
O.-phenyl  salicylic  acids  (diphenyl  ether  ortho-ca.rbox.ylic 
acids)  in  a  manner  exactly  similar  to  that  employed 
in  the  case  of  acridone. 


THE  THIOXANTHONES 

/\/S 

i 

These   contain   the   structure 


\/\ 


and 


can  be  obtained  from  the  phenylated  thiosalicylic 
acids,1  just  as  the  xanthones  are  obtained  from  pheny- 
lated salicylic  acid.  A  more  convenient  method, 
however,  has  recently  been  published  by  Smiles  and 
his  co-workers.2  This  consists  in  condensing  thio- 
salicylic acid  with  an  aromatic  compound  in  the  presence 
of  concentrated  sulphuric  acid.  Apparently  the  first 
reaction  is  the  formation  of  a  sulphoxylic  acid,  which 
then  condenses  with  the  second  component  with  loss 
of  water,  an  aryl  thiosalicylic  acid  being  formed. 

1  B.  43,  584;  44,  3125. 

2  Soc.  97,  1290  ;  99,  640. 


MISCELLANEOUS  TYPES  271 

This  in  turn  loses  another  molecule  of  water  to  form 
the  thioxanthone  : 


SH 


- 

I     UCOOH 


COJOH 


In  some  cases  fo's-thioxanthones  are  formed.     The 
disulphides  x  react  in  an  exactly  similar  way. 


THE  PHENOXAZINES 

These  compounds  contain  the  structure 


\/\ 


NH- 


and  can  be  obtained  by  heating  the  o^o-amino-phenols 
with  the  pyrocatechols. 

PREPARATION  OF  PHENOXAZINES  Equal  parts  of 
o.-aminophenol  and  pyrocatechol  are  heated  for  forty  hours  to 
26o°-28o°.  The  cooled  melt  is  extracted  several  times  with 
water  and  then  with  boiling  dilute  caustic  soda.  The  dried 
residue  is  extracted  with  ether  in  a  Soxhlet  apparatus,  the 
ethereal  extract  washed  with  dilute  caustic  soda,  boiled  with 
animal  charcoal,  and  the  ether  removed  by  distillation  from 


Soc.  97,  1290;   99,  641. 


2  B.  20,  943. 


272      PREPARATION  OF  ORGANIC  COMPOUNDS 

the  water-bath.      The  residue   is  then  recrystallised    several 
times  from  dilute  alcohol.     Colourless  leaflets  melting  at  148°. 

The  technically  important  oxazine  dyes  are  quinonoid 
in  character  and  have  the  structure  : 


O 


Cl 
.O, 


R2N 


or 


and 


\/\/ 


\/\N/\/ 

O 


N 

They  are  prepared  by  condensing  quinone  dichlorimides, 
nitroso-phenols,  or  salts  of  nitroso-diarylamines  with 
phenols  or  tertiary  ammo-phenols.  The  reaction 
usually  takes  place  simply  by  heating  p.-mtroso- 
dimethylaniline  hydrochloride  (three  molecules)  with 
the  phenol  (two  molecules)  in  the  presence  of  some 
suitable  solvent,  such  as  alcohol  or  glacial  acetic  acid. 
One  molecule  of  the  nitroso-amine  is  reduced  during 
the  reaction  to  the  ^.-diamine. 

PREPARATION  OF  GALLOCYANINE.1  Ten  grammes  of 
gallic  acid  and  17  grm.  of  £.-nitroso-dimethylaniline  hydro- 
chloride  are  boiled  under  a  reflux  condenser  with  200  c.c.  of 
alcohol  until  a  drop  of  the  liquid  placed  on  filter-paper  gives  a 
dark  blue  spot  with  no  yellow  rim,  and  after  continuing  the 
heating  for  a  time  an  exactly  similar  spot  is  obtained.  The 
alcohol  is  then  distilled  off  from  the  water-bath,  the  residue 
evaporated  to  dry  ness  and  then  boiled  with  200  c.c.  of  water. 
The  dyestuff  is  filtered  off  and  dried  in  a  vacuum  desiccator. 
It  forms  a  bronze-coloured  powder  which  dyes  wool  bluish 
violet  on  a  chrome  mordant. 


1  Cain  and  Thorpe,  "Synthetic  Dyestuffs  "  (1905),  p.  258. 


HO 


OH 

x\ 


MISCELLANEOUS  TYPES 
OH 


273 


OH 


NMe2HCl 


HOr 


O 


HO 


HO 


O 


=        2 


or 


N(CH3)2 


co- 


NH« 


\/\l 


3HC1  +  3H20 


CO 


/ 

NMe2 


PREPARATION  OF  MELDOLA'S  BLUE.1  Twenty-one 
grammes  of  /3-naphthol  and  53  grm.  of  ^.-nitroso-dimethyl 
aniline  hydrochloride  are  boiled  on  the  water-bath  in  alcoholic 
solution  for  eight  to  ten  hours.  The  dyestuff  is  then  precipi- 
tated as  its  zinc  chloride  double  salt  by  adding  zinc  chloride 
solution  until  no  more  precipitation  takes  place.  It  is  collected 
and  dried  in  a  vacuum  desiccator.  It  forms  a  dark  violet 
powder  which  dyes  cotton  blue  on  a  tannin  and  tartar  emetic 
mordant.  It  has  the  structure  : 

Cl 


ClMe2N 


Me2N 


\/ 


or 


1  Cain  and  Thorpe,  "  Synthetic  Dyestuffs  "  (1905),  p.  257. 


18 


274      PREPARATION  OF  ORGANIC  COMPOUNDS 

THE  THIAZINES 

The  thiazines  or  thiodiphenylamines  are  the  sul- 
phur analogues  of  the  phenoxazines  and  contain  the 

/\/NH\/\ 

structure 

\/\s 

They  are  readily  obtained  in  excellent  yield  by  heating 
the  diphenylamines  with  sulphur  in  the  presence  of 
anhydrous  aluminium  chloride,  iodine,  or  other  contact- 
substances.  The  reaction  is  carried  out  with  or  without 
a  solvent. 

PREPARATION  OF  THIODIPHENYLAMINE.1  Seventeen 
grammes  of  diphenylamine,  6-5  grm.  of  sulphur,  and  2-5  grm. 
of  anhydrous  aluminium  chloride  are  melted  together.  The 
reaction  sets  in  with  brisk  evolution  of  sulphuretted  hydrogen 
at  I40°-I50°,  and  is  moderated  by  lowering  the  temperature  a 
few  degrees.  When  the  reaction  has  slackened,  the  tempera- 
ture is  raised  to  160°  for  a  time.  The  cooled  melt  is  ground 
up,  and  extracted,  first  with  water  and  then  with  dilute 
alcohol.  The  residue  consists  of  almost  pure  thiodiphenyl- 
amine.  It  may  be  recrystallised  from  alcohol.  Yellowish 
eaflets  melting  at  180°.  The  yield  is  93  per  cent. 

When  an  amine,  or  a  mixture  of  two  amines  or  a 
mixture  of  an  amine  and  a  phenol  is  heated  with  a 
suitable  catalyst  (I,  A1C13,  &c.,  see  p.  231),  a  diaryl- 
amine  is  formed.  If  sulphur  is  also  present  a  thio- 
diarylamine  results.  The  yields  are  excellent.2 

When    thiodiphenylamine    is    nitrated,    a    dinitro- 

/\/NH\/\ 
sulphoxide  is  obtained,3  and  when 


this  is  reduced  it  yields  a  diamino-thiazine  : 

1  Pat.  Anm.  Kl.  12  q.  17,228,  17,440,  17,995. 

2  Pat.  Anm.  Kl.  12.  O.  K.  44,367. 

3  A.  230,  73. 


MISCELLANEOUS  TYPES 


275 


NH9 


NH, 


This  is  leuco-ihiomne  (Laut's  violet),  the  dyestuff 
itself  being  the  chloride  of  the  oxidised  product,  and 
having  the  formula  : 


\/\ 


C1NH2 


or 
NH2         NH2 


(The  oxidation  of  the  leuco-compound  takes  place  with 
great  ease  when  its  solutions  are  exposed  to  the  air.) 

These  thiazine  dyes  are  also  obtained  when 
/>.-diamines  are  oxidised  by  ferric  chloride  in  the 
presence  of  sulphuretted  hydrogen  (test  for  />.-diamines), 
and  when  a  ^.-diamine  and  a  monamine  are  oxidised 
in  the  presence  of  sodium  thiosulphate  and  zinc 
chloride. 

PREPARATION  OF  METHYLENE  BLUE.*  Fifteen 
grammes  of  £.-nitroso-dimethylaniline  or  a  corresponding 
quantity  of  the  hydrochloride  are  dissolved  in  55  grm.  of  con- 
centrated hydrochloric  acid  and  40  c.c.  of  water,  and  then 
reduced  in  the  cold  to  the  corresponding  diamine  by  means  of 
zinc  dust.  Sufficient  zinc  dust  must  be  used  to  neutralise 
the  whole  of  the  hydrochloric  acid.  The  reduced  solution  is 
filtered  from  excess  of  zinc  dust,  diluted  to  500  c.c.,  and  then 
1 6  grm.  of  dimethylaniline  dissolved  in  exactly  one  equivalent 
of  hydrochloric  acid  added.  Fifty  grammes  of  sodium 
thiosulphate,  and  then  25  grm.  of  sodium  or  potassium 
bichromate  (both  in  concentrated  solution),  are  next  added 
and  the  whole  boiled  for  two  hours.  After  cooling  somewhat, 
150  grm.  of  30  per  cent,  sulphuric  acid  are  added  and  the  whole 
boiled  until  all  the  sulphur  dioxide  has  been  expelled.  The 

i  D.R.P.  38,573- 


276     PREPARATION  OF  ORGANIC  COMPOUNDS 

solution  now  contains  leuco-methyleue  blue.  This  is  oxidised 
to  the  dyestuff  by  adding  a  concentrated  solution  of  8  grm.  of 
neutral  sodium  chromate,  and  the  colour  then  precipitated  by 
adding  salt.  It  is  collected,  dissolved  in  a  little  boiling  water 
containing  hydrochloric  acid,  and  again  salted  out.  It  forms  a 
dark-coloured  powder  with  a  strong  metallic  lustre.  It  dyes 
cotton  blue  on  a  tannin  mordant.  The  mechanism  of  the  above 
preparation  is  indicated  by  the  following  equations  : 


Me£N 


NH2 
H2S208  +0 


NH2 


H 


Me2N 


\/\ 


S-S03H 


\/ 


NMe2 


J    +20 


N 


S03 


HC1  +  O 


N 


Methylene  blue 


THE  AZINES 

The  azines  or  quinoxalines  have  the  structure  : 
»***.      s  /\     /N^ 


or 


\/\N/\ 


and  can  be  obtained  from  the  o.-diamines  by  con- 
densing with  a-diketones,  such  as  benzil,  &c.,  glyoxal, 


MISCELLANEOUS  TYPES  277 

a-aldehydic  or  ketonic  acids,  e.g.  glyoxylic  acid, 
pyruvic  acid,  or  with  oxalic  acid.  The  reactions, 
as  a  rule,  take  place  with  great  ease  merely  by 
boiling  the  diamine  with  the  second  component  in 
some  suitable  solvent,  such  as  glacial  acetic  acid. 
The  compounds  above  cited  all  give  rise  to  quinoxalines, 

,N< 

e.g.    compounds    of    the    type  The 


true   azines,    the   phenazines  are  of 

\/\N/\/ 

greater  importance,  and  are  obtained  by  condensing 
the  o.-diamines  with  o^Ao-quinones,  such  as  phen- 
anthraquinone,  /3-naphthoquinone,  &c.  The  reaction 
takes  place  with  great  ease,  and  as  the  azines  are 
well-defined  crystalline  compounds,  which  often  show 
characteristic  colour  reactions  with  acids,  their  forma- 
tion provides  a  ready  means  of  identifying  the  ortho- 
diamines  which  are  frequently  formed  when  an  azo- 
dye  is  reduced.  The  condensation  takes  place  either  on 
boiling  the  diamine  and  the  quinone  (usually  phenanthra- 
quinone)  in  glacial  acetic  acid  solution  for  a  short  time, 
or  if,  as  is  often  the  case,  the  diamine  cannot  be  readily 
isolated,  the  phenanthraquinone  is  dissolved  in  sodium 
bisulphite,  excess  of  sodium  acetate  added,  and  the  solu- 
tion thus  obtained  added  to  the  boiling  aqueous  solution 
of  the  diamine  rendered  slightly  acid  with  acetic  acid. 

ISOLATION     OF     AN     AZINE     FROM     CONGO     RED.i 

Seven  grammes  of  Congo  Red  are  dissolved  in  a  little  boiling 
water  and  the  solution  made  strongly  alkaline  with  ammonia. 
Zinc  dust  is  then  sifted  in  until  the  red  colour  vanishes. 
After  cooling,  the  benzidine  (see  below)  and  unchanged  zinc 
dust  are  filtered  off,  the  filtrate  acidified  with  acetic  acid, 
heated  to  boiling,  and  then  treated  rapidly  with  a  warm  solution 

1  B.  19,  1721. 


278      PREPARATION  OF  ORGANIC  COMPOUNDS 

of  4  grm.  of  phenanthraquinone  in  aqueous  sodium  bisulphite 
to  which  excess  of  sodium  acetate  has  been  added.  The  azine 
begins  to  separate  almost  at  once.  When  the  separation  is 
complete  the  precipitate  is  collected,  washed  with  cold  water, 
dissolved  in  hot  water,  an  equal  volume  of  alcohol  added 
and  then  a  drop  of  caustic  soda  solution.  On  cooling,  the 
sodium  salt  separates  out  as  silky  yellow  needles  which  give  a 
violet  solution  in  concentrated  sulphuric  acid,  changing  orange - 
yellow  on  dilution.  The  formation  of  the  azine  takes  place 
as  follows  : 

NH2 


— N!H2  O  =  1C 

1 \/\ 


Congo  red 


/\/\N/\/         \ 


\/ 

The  important  dyestuffs,  the  eurhodines,  apo- 
safranines,  safranines,  indulines,  and  nigrosines  are  all 
azines.  For  the  methods  whereby  they  are  prepared 
the  reader  is  referred  to  works  on  tinctorial  chemistry.1 

1  Cain  and  Thorpe,  "  Synthetic  Dyestuffs  "  (1905)  ;  Schultz, 
"  Chemie  des  Steinkohlenteers  "  (1901);  Mohlau  u.  Bucherer, 
"  Farbenchemisches  Praktikum"  (1908). 


MISCELLANEOUS  TYPES 


279 


THE  QUINOLINES  AND  ISOQUINOLINES 

The  quinolines  and  isoquinolines  respectively  contain 


the  groups 


and 


N 


The  latter  compounds  are  somewhat  difficult  to 
prepare,  and  will  not  be  further  mentioned. 

The  quinolines  themselves  are  readily  obtained  by 
several  methods,  viz.  : 

(i)  SKRAUP'S  SYNTHESIS.  This  is  the  most  gene- 
rally employed  method,  and  is  of  universal  applica- 
tion to  all  primary  aromatic  amines  which  have  one 
carbon  atom  in  the  ortho-  position  to  the  amino-group 
free.  The  synthesis  is  carried  out  by  heating  the  amine 
with  glycerine  in  the  presence  of  concentrated  sulphuric 
acid  and  an  oxidising  agent.  The  reaction  takes  place 
in  the  following  stages  : 


CH2OH .  CHOH .  CH2OH 


— 2H2O 


CH 

I 
CH 


JO  H2iN 


CH 


CH2 


o 


CH 


N 


\/\/ 

N 


CH 
CJH 


As  an  oxidising  agent  it  is  usual  to  employ  the  nitro- 
compound  corresponding  to  the  amine.  Thus  if  the 
base  is  aniline,  the  oxidising  agent  is  nitrobenzene; 
if  toluidine,  the  corresponding  nitrotoluene  is  used,  &c. 
Better  results,  however,  are  generally  obtained  by  using 
arsenic  acid  as  an  oxidising  agent. 


280      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  QUINOLINE  (C9H7N).*  Twenty-four 
grammes  of  nitrobenzene,  38  grm.  of  aniline,  120  grm.  of 
glycerine,  and  100  grm.  of  concentrated  sulphuric  acid  are  well 
shaken  together  and  then  cautiously  heated  under  a  reflux 
air-condenser  on  the  sand-bath  until  a  reaction  sets  in  with 
evolution  of  white  fumes.  The  flask  is  at  once  removed  from 
the  sand-bath  and  the  reaction  allowed  to  proceed  without 
external  heating.  When  the  reaction  has  subsided,  the  whole 
is  heated  to  gentle  boiling  for  two  hours,  cooled,  and  diluted 
with  water.  Excess  of  nitrobenzene  is  distilled  off  in  steam, 
the  residue  made  alkaline  with  caustic  soda  and  again  distilled 
in  steam,  when  a  mixture  of  quinoline  and  aniline  passes  over. 
In  order  to  separate  these  the  distillate  is  cooled  to  5°  by  the 
addition  of  ice,  made  acid  with  sulphuric  acid,  and  then 
treated  slowly  with  a  concentrated  solution  of  sodium  nitrite 
until  the  liquid  gives  a  blue  coloration  to  starch-iodide  paper 
after  standing  for  ten  minutes.  The  solution  is  then  boiled 
for  a  quarter  of  an  hour  in  order  to  convert  the  diazo- 
benzene  chloride  into  phenol,  made  strongly  alkaline,  and  again 
distilled  in  steam.  The  distillate  is  extracted  with  ether,  the 
ethereal  solution  dried  with  solid  caustic  potash,  and  the  ether 
removed  on  the  water-bath.  The  residue  is  then  fractionated. 
Colourless  or  pale  yellow  liquid  boiling  at  237°.  The  yield  is 
60  per  cent. 

PREPARATION  OF  o  -NITROQUINOLINE  (C9H6O2N2).2 
One  hundred  grammes  of  concentrated  sulphuric  acid,  5 1*5  grm. 
of  arsenic  acid,  1 10  grm.  of  glycerine,  and  50  grm.  of  o.-nitrani- 
line  are  well  shaken  together  and  cautiously  heated  under  a 
reflux  condenser  until  a  reaction  sets  in.  The  flask  is  removed 
from  the  sand-bath  until  the  reaction  has  moderated,  and 
the  whole  then  boiled  gently  for  three  hours.  After  cooling, 
the  product  is  diluted  with  a  large  volume  of  water,  allowed  to 
stand  over-night,  and  then  filtered.  The  filtrate  is  treated 
cautiously  with  caustic  soda  until  a  brown  precipitate  makes 
its  appearance.  The  first  portion  of  this  precipitate  is  removed 
by  filtration  and  discarded,  and  the  precipitation  then  completed 
by  adding  caustic  soda  to  the  filtrate  until  alkaline.  The 
crude  nitro quinoline  thus  obtained  is  collected,  washed  with 
water,  dissolved  in  alcohol,  and  boiled  with  animal  charcoal. 
On  slowly  adding  water  to  the  alcoholic  solution  0. -nitro - 

1  M.  i,  316  ;   2,  139  ;   B.  14,  1002.  2  B.  29,  705. 


MISCELLANEOUS  TYPES  281 

quinoline  separates  out  in  the  crystalline  form.  It  forms 
monoclinic  needles  which  melt  at  88°-89°.  The  yield  is  56  per 
cent. 

A  variation  of  the  above  synthesis  is  due  to  Doebner 
and  Miller.  They  showed  that  quinolines  can  be 
obtained  when  anilines  (one  molecule)  are  condensed 
with  two  molecules  of  acetaldehyde  or  of  an  aldehyde  of 
the  general  formula,  CHO.CH2R,  where  R  represents 
an  alkyl  or  aryl  group.  The  condensation  takes  place 
in  the  presence  of  sulphuric  or  hydrochloric  acid. 
Instead  of  using  two  molecules  of  the  same  aldehyde,  a 
mixture  of  two  aldehydes  or  of  an  aldehyde  and  a 
ketone  can  be  used,  or  the  benzylidene  derivative  can  be 
isolated  from  the  aldehyde  and  the  base,  and  this 
then  condensed  with  another  aldehyde  or  ketone  by 
means  of  zinc  chloride.  The  reaction  takes  place 
especially  easily  when  naphthylamine  is  condensed 
with  pyruvic  acid  and  an  aldehyde,  and  the  production 
of  a-alkyl  cinchoninic  acids  can  be  used  as  a  test  for 
aldehydes.  The  reaction  takes  place  as  follows  : 


where  R  is  an  alkyl  or  aryl  group,  and  R'  and  R"  an  alkyl 
or  aryl  group  or  a  hydrogen  atom.  In  the  case  of  the 
above-mentioned  reaction  with  naphthylamine,  pyruvic 


282      PREPARATION  OF  ORGANIC  COMPOUNDS 
acid,  and  an  aldehyde,  a  naphthocinchoninic  acid  of  the 


COOH 


formula 


is  produced.  The  hydrogen 


evolved  during  this  synthesis  often  partially  reduces 
the  quinoline  to  a  tetrahydroquinoline. 

PREPARATIONOFa-METHYLQUINOLINE(QUINALDINE), 

Thirty  grammes  of  aniline,  60   grm.   of 


N  =  C.CH3 

technical  concentrated  hydrochloric  acid,  and  20  grm.  of 
zinc  chloride  are  heated  on  the  water-bath  under  a  reflux 
condenser,  and  25  grm.  of  acetaldehyde  slowly  dropped  in 
during  about  two  hours.  When  all  the  aldehyde  has  been 
added,  the  whole  is  boiled  on  the  sand-bath  for  an  hour  and  a 
half,  made  alkaline  with  caustic  soda,  and  distilled  in  steam. 
The  crude  quinaldine  is  collected  and  fractionally  distilled. 
Colourless  liquid  boiling  at  247°. 

PREPARATION  OF  a-PHENYL-a-NAPHTHOCINCHONINIC 
ACID.2  Twelve  grammes  of  pyruvic  acid  and  15  grm.  of 
benzaldehyde  are  dissolved  in  alcohol,  and  an  alcoholic  solution 
of  20  grm.  of  a-naphthylamine  added  through  a  reflux  con- 
denser in  the  course  of  a  few  minutes.  A  vigorous  reaction 
sets  in,  and  when  this  has  subsided  the  whole  is  boiled  on  the 
water-bath  for  five  hours.  After  cooling,  the  contents  of  the 
flask  are  filtered,  the  precipitate  washed  with  alcohol,  and  then 
dissolved  in  hot  dilute  caustic  soda.  When  the  solution  has 
cooled  to  50°  it  is  filtered,  the  precipitate  rejected,  and  the 
filtrate  allowed  to  cool.  The  sodium  salt  of  the  acid  separates 
in  colourless  needles,  and  is  recrystallised  several  times  from 
boiling  water. 

The  free  acid  can  be  obtained  by  treating  the  sodium  salt 

1  B.  16,  2465  ;  D.R.P.  28,217.  2  A.  249,  no;  281,  i. 


MISCELLANEOUS  TYPES 


283 


with  hydrochloric  acid,  and  then  recrystallising  the  precipi- 
tate from  a  mixture  of  alcohol  and  acetone.  It  forms  lemon- 
yellow  needles  which  melt  with  decomposition  at  about  300°. 
The  yield  is  30  per  cent. 

COOH 


OCHPh 


COOH 


/Y  NCH 

I  .CPh  +  H2  +  H20 

N/       \K[S 


V 

The  hydrogen  reduces  part  of  the  quinoline  to  a  tetrahydro- 
compound. 

The  corresponding  a-phenyl-/3-naphthocinchoninic  acid  is 
obtained  from  /3-naphthylamine  in  exactly  the  same  way. 
The  reaction,  however,  is  more  violent,  and  hence  the  solution 
should  not  be  too  concentrated.  It  is  best  purified  through 
its  ammonium  salt.  It  crystallises  in  lemon-yellow  needles 
from  alcohol  containing  a  little  hydrochloric  acid,  and  from 
mixtures  of  amyl  alcohol  and  glacial  acetic  acid  in  colourless 
needles.  It  melts  with  decomposition  at  296°. 

Both  of  the  above  compounds  can  also  be  prepared  by  allowing 
an  ethereal  solution  of  a  molecular  mixture  of  the  three 
components  to  stand  for  twenty-four  hours  at  the  ordinary 
temperature. 

(ii)  BAEYER'S  SYNTHESIS.  The  second  important 
synthesis  of  quinoline  compounds  starts  out  from 
primary  aromatic  amines  containing  a  side-chain  in  the 


284      PREPARATION  OF  ORGANIC  COMPOUNDS 

ortho-  position,  consisting  of  three  carbon  atoms,  the 
last  of  which  carries  an  oxygen  atom,  e.g.  o.-amino- 
cinnamic  acid,  o.-aminocinnamic  aldehyde,  &c.  The 
condensation  usually  takes  place  very  readily  by  merely 
heating  in  some  suitable  solvent.  The  reaction  can 
often  be  carried  out  by  starting  with  the  corresponding 
nitro-compound  and  heating  it  with  alcoholic  ammo- 
nium sulphide. 

PREPARATION  OF  CARBOSTYRIL.1  o.-Nitrocinnamic 
ester  in  portions  of  30-40  grm.  is  heated  with  an  excess  of 
saturated  alcoholic  ammonium  sulphide  for  some  hours  on 
the  water-bath  in  closed  vessels  (soda-water  bottles  can  be 
used  conveniently).  After  cooling,  some  of  the  ammonium 
salt  of  carbostyril  will  have  separated  out  and  is  collected. 
The  alcoholic  filtrates  are  acidified,  evaporated  to  dryness, 
and  the  residue  extracted  with  hot,  very  dilute  caustic  soda. 
After  filtering,  the  alkaline  liquors  are  saturated  with  carbon 
dioxide,  which  causes  the  carbostyril  to  be  precipitated.  It 
melts  at  199°. 

CH\          /\/CH\ 

CH  CH 


C  =  0 


C  =  0 


or 


Lactam  form 


Carbostyril 


C  =  0 

I 

NHJHOEtj 
CH^ 

CH 
C.OH 


N  * 
Lactime  form 


There  are  two  important  variations  of  this  synthesis, 
viz.  (a)  the  o.-amino-benzaldehydes  or  o.-amino-benzo- 
ketones  are  condensed  with  compounds  containing  the 
group  — CH2 — CO — ,  viz.  aldehydes,  ketones,  aceto- 

1  B.  14,  1916. 


MISCELLANEOUS  TYPES  285 

acetic   ester,  &c. ;    and    (b)   o.-toluidine  is  condensed 
with  glyoxal  or  pyruvic  acid  : 

H 


,CiH2Oi=C.CH 


C.CHg 

C.OH 


Pyruvic  acid 


CH 


CH 


N* 
CH, 

N' 


CH 


Glyoxal 

Of  these  variations,  the  first  is  the  more  important. 
The  condensation  takes  place  very  readily  at  the  ordi- 
nary temperature  or  on  gently  warming  the  reacting 
substances  in  alcoholic  solution  in  the  presence  of  a 
trace  of  caustic  soda. 

PREPARATION  OF  QUINALDINE.1  One  molecule  of 
o.-amino-benzaldehyde  and  rather  more  than  one  molecule  of 
pure  acetone  are  dissolved  in  alcohol,  and  a  few  drops  of  alco- 
holic caustic  soda  added.  The  condensation  takes  place  at 
the  ordinary  temperature.  The  quinaldine  is  collected  by 
steam  distillation  and  washed  with  water  until  free  from 
acetone.  B.P.  247°. 
,H 


/ 


N|H2  Of 


C.CH3 


1  B.  16,  1834. 


CH 
C.CH3 


N 


286      PREPARATION  OF  ORGANIC  COMPOUNDS 

PREPARATION  OF  a-PHENYL  QUINOLINE.1  o.-Amino- 
benzaldehyde  and  acetophenone  (i£  molecules)  are  dissolved  in 
aqueous  alcohol,  a  few  drops  of  caustic  soda  added,  and  the 
whole  warmed  for  a  short  time.  It  is  then  acidified  with 
hydrochloric  acid,  excess  of  acetophenone  removed  by  steam- 
distillation,  and  the  residue  made  alkaline  with  caustic  soda. 
The  precipitate  is  recrystallised  from  dilute  alcohol.  Colourless 
needles  melting  at  84°. 

PREPARATION  OF  QUINALDINE-/3-CARBOXYLIC 
ESTER.2  An  aqueous  solution  of  o.-aminobenzaldehyde 
(  one  molecule)  and  an  alcoholic  solution  of  acetoacetic  ester 
(  one  molecule)  are  mixed  and  allowed  to  stand  at  the  ordinary 
temperature.  The  separation  of  the  condensation  product 
starts  almost  at  once.  When  nothing  more  separates,  the 
long  white  needles  are  collected  and  recrystallised  from  dilute 
alcohol.  They  melt  at  71°. 


CHIO 


N|H2 


HgjC.COOEt 


;;C.CH3 


CH, 


N 


C.C02Et 
C.CH 


When  o.-amino-benzaldehyde  and  acetoacetic  ester 
are  heated  together  without  a  solvent  to  160°  the 
reaction  takes  a  different  course. 


HgC.CO.CHa 
-CO 


CEL 


>C.CO.CH3 


,CH« 


or 


,CO 

Lactam  form 
1  Loc.  cit. 


*C.CO.CH3 
X.OH 


/S-Acetyl  carbostyril 


N  ' 
Lactime  form 


2  B.  16,  1835. 


MISCELLANEOUS  TYPES 


287 


The  solid  product  is  washed  with  ether  to  remove  excess  of 
acetoacetic  ester,  and  then  recrystallised  from  glacial  acetic 
acid.  Colourless  needles  melting  at  232°. 

(iii)  NIEMENTOWSKI'S  SYNTHESIS.  An  interest- 
ing synthesis  of  the  a-aryl-y-oxyquinolines  consists  in 
condensing  anthranilic  acid  with  acetophenones.  The 
condensation  takes  place  on  prolonged  heating  (two 
to  five  days)  at  I2O°-I5O°.  It  is  really  a  variation 
of  the  above. 

PREPARATION    OF    a-PHENYL-y-OXYQUINOLINE.*     A 

mixture  of  equal  parts  of  anthranilic  acid  and  acetophenone 
is  heated  to  I2o°-i3o°  for  two  to  three  days.  The  cooled 
melt  is  made  alkaline  with  dilute  caustic  soda,  extracted  with 
ether,  the  aqueous  portion  acidified  with  acetic  acid,  and  again 
extracted  with  ether.  The  ethereal  extracts  are  discarded  and 
the  aqueous  portion  of  the  liquid  filtered.  The  precipitate  is 
well  washed  with  water,  dissolved  in  dilute  caustic  soda,  and 
the  solution  saturated  with  carbon  dioxide.  The  quinoline 
derivative  separates  out  and  is  recrystallised  from  alcohol. 
It  melts  at  about  250°. 


COiOH 


X/SL 


H!CH2 


OiC.Ph 


CH, 


Ph 


OH 
C, 


or 


CH 
CPh 


Ketonic  form  Enolic  form 

a-Phenyl-7-oxyquinoline 


B.  27,  1396. 


288      PREPARATION  OF  ORGANIC  COMPOUNDS 

THE  TRIPHENYL  METHANE  GROUP 

The  triphenyl  methane  hydrocarbons  are  best 
obtained  by  condensing  three  molecules  of  an  aromatic 
hydrocarbon  with  chloroform  in  the  presence  of  alu- 
minium chloride,  as  described  on  p.  43.  An  inte- 
resting synthesis  also  consists  in  heating k  the  benz- 
hydrols  with  benzene  and  phosphorus  pentoxide1  to 
140°. 


Triphenylmethane 

The  most  important  members  of  the  group  are  the 
triphenyl  methane  dyes.  These  may  be  divided  into 
five  classes,  viz. :  (i)  The  malachite  green  group,  derived 
from  ^.2-diamino-triphenyl  methane.  (2)  The  rosaniline 
group,  derived  from  /).3-triamino-triphenyl  methane. 
(3)  The  benzeins,  derived  from  ^.2-dioxy- triphenyl 
methane.  (4)  The  aurines  or  rosolic  acids,  derived  from 
^>.3-trioxy-triphenyl  methane.  (5)  Phthalems,  rhod- 
amines,  and  pyronines,  derived  from  dioxy-  or  diamino- 
triphenyl  methane  carboxylic  acids. 

It  is  impossible  to  give  more  than  a  rough  outline 
of  the  methods  employed  in  preparing  these  colours. 
For  a  fuller  discussion  the  reader  is  referred  to  works 
dealing  with  tinctorial  chemistry.2 

THE  MALACHITE-GREEN  DYES.  The  di-£.-amino- 
triphenyl  methanes  are  the  leuco-compounds  of  this 
group  of  colouring-matters.  On  oxidation  they  pass 
into  the  carbinols  (colourless),  which  in  the  presence 

1  B.  7,  1204. 

2  Such    as    Cain    and    Thorpe,    "Synthetic    Dyestuffs "  ; 
Schultz,  "Chemie  des  Steinkohlenteers,"  vol.  ii;    Mohlau  u. 
Bucherer,  "  Farbenchemisches  Praktikum." 


MISCELLANEOUS  TYPES  289 

of  acids  lose  a  molecule  of  water  and  pass  into  the 
dyestuffs  proper  : 

NH2C1 
NH2  NH2  || 

/\  /\ 


\/ 

O  HC1  II 

C6H5 .  C .  H       _»      C6H6 .  C .  OH       — >       C6H5— C  +  H2O 

A  A 


\/  \/  \/ 

NH2  NH2  NH2 

The  free  bases  are  unstable.  Thus  on  adding  one 
equivalent  of  an  alkali  to  malachite  green,  a  coloured 
solution  of  the  ammonium  base  is  obtained,  having  high 
electrical  conductivity.  On  standing,  however,  the 
solution  becomes  colourless,  and  the  conductivity 
simultaneously  falls,  owing  to  the  formation  of  the 
non-ionised  carbinol.1  The  change  may  be  represented 
thus  : 


/C6H4NMe2 

Ph.C  -~     Ph.C/  - 

XC6H4  =  NMe2Cl  ^C6H4  =  NMe2OH 

Malachite  green  Ammonium  base 

/C6H4NMe2 
Ph.C^-OH 

\C6H4NMe2 

Carbinol 

The  dyes  of  this  series  are  obtained  by  condensing 
benzaldehyde,  benzhydrol,  or  benzotrichloride  with 
the  hydrochloride  of  an  amine  by  means  of  phosphorus 

1  B.  33,  303- 

19 


2QO      PREPARATION  OF  ORGANIC  COMPOUNDS 

pentoxide  or  zinc  chloride.  The  resulting  dianuno- 
triphenyl  methane  is  then  oxidised,  usually  by  means 
of  lead  oxide,  to  the  carbinol,  which  in  the  presence  of 
acids  at  once  loses  water  to  form  the  dyestuff  (see 
above).  The  dyes  are  usually  isolated  as  the  zinc 
chloride  double  salt.  The  amine  always  condenses  in 
the  para-  position  to  the  amino-group. 

PREPARATION  OF  MALACHITE  GREEN.*  Twenty 
grammes  of  benzaldehyde,  50  grin,  of  dimethyl  aniline,  and 
20  grm.  of  powdered  anhydrous  zinc  chloride  are  heated  on 
the  water-bath  in  a  basin  for  four  hours,  the  whole  being 
well  stirred  at  frequent  intervals.  The  melt  is  liquefied  by 
the  addition  of  boiling  water,  transferred  to  a  flask  and  distilled 
in  steam  until  no  more  unchanged  dimethylaniline  passes  over. 
On  cooling,  the  leuco-ba.se  adheres  to  the  flask,  and  the  aqueous 
zinc  chloride  solution  is  decanted.  The  base  is  washed 
several  times  with  cold  water  by  decantation,  and  then  recrys- 
tallised  from  boiling  alcohol.  As  it  separates  rather  slowly 
it  is  advisable  to  allow  the  alcoholic  solution  to  stand  over- 
night before  collecting  the  crystals.  If  the  substance  separates 
as  an  oil  it  is  a  sign  that  the  solution  has  been  too  concen- 
trated, and  the  base  must,  therefore,  be  again  dissolved  with 
the  addition  of  more  alcohol.  The  leuco-ba.se  separates  as 
colourless  needles,  a  further  quantity  of  which  may  be  obtained 
by  concentrating  the  alcoholic  mother-liquors.  The  yield  is 
almost  quantitative.  It  is  oxidised  to  the  dye  as  follows  : 
Ten  grammes  are  dissolved  in  dilute  hydrochloric  acid  contain- 
ing 2.7  grm.  of  hydrogen  chloride  (this  must  be  exact),  the 
solution  diluted  to  800  c.c.  and  then  well  cooled  by  the  addition 
of  ice.  A  thin  paste  of  exactly  7.4  grm.  of  pure  lead  peroxide 
is  added  little  by  little  during  five  minutes,  and  the  whole 
shaken  for  another  five  minutes.  (The  lead  peroxide  should 
be  freshly  prepared.)  The  lead  is  then  precipitated  by  sodium 
sulphate  (about  10  grm.  of  the  salt  in  50  c.c.  of  water),  the  lead 
sulphate  removed  by  filtration,  and  a  concentrated  solution 
of  8  grm.  of  zinc  chloride  added  to  the  filtrate.  On  adding 
saturated  salt  solution  the  dye  is  precipitated  as  its  zinc 
chloride  double  salt.  This  is  collected,  dissolved  in  water, 
and  again  salted  out.  It  forms  yellowish  green  crystals.  The 
yield  is  about  80  per  cent. 

1  A.  206,  122. 


MISCELLANEOUS  TYPES  291 

^CeH*  [4]NMe2  //C6H4NMe2 

Ph.CHO     —     PhCH  Ph.C.OH  — 

\C6H4[4]NMe2  \C6H4NMe2 

Leuco  base 

/C6H4[4]NMe2 
Ph.C/ 

^C6H4[4]NMe2Cl 

The  zinc  chloride  salt  has  the  formula  : 
C6H4NMe2 


f  x642         v 

(C6H6.C/  . 

^  / 


2ZnCl2.H20 

THE  ROSANILINE  DYES.  Just  as  the  £2.-diamino- 
triphenyl  methanes  are  the  /^wco-compounds  of  the 
malachite-green  dyes,  so  are  the  />3-triamino-triphenyl 
methanes  the  /^co-compounds  of  the  rosaniline 
colours,  into  which  they  pass  by  oxidation  and  subse- 
quent loss  of  water  in  the  presence  of  acids. 

The  rosanilines  are  obtained  by  methods  analogous  to 
those  employed  in  the  preparation  of  the  malachite 
greens,  viz.  : 

(i)  By  condensing  the  ^.-amino-benzaldehydes  with 
amino-compounds.  It  is  usual  not  to  isolate  the  amino- 
aldehyde,  but  to  condense  the  amino-hydrocarbon  with 
a  ^.-toluidine  in  the  presence  of  an  oxidising  agent,  e.g.  : 


i HJ/" ^-NH, 

T 

(NHaCjHtk.CH 

Lento-compound 

1° 

TT/"*1 

:C(C6H4NH2)2     ~—     (NH2.C6H4)3.COH 


Dyestuff  Carbinol  base 


292   PREPARATION  OF  ORGANIC  COMPOUNDS 

Instead  of  two  molecules  of  the  same  amine,  molecules 
of,  two  different  amines  can  be  condensed  with  the 
aldehyde,  provided  that  the  far  a-  position  to  the  ammo- 
group  is  unoccupied.  Thus  magenta  is  obtained  by 
oxidising  a  mixture  of  aniline  and  o.-  and  ^.-toluidine 
("aniline  oil  for  red").  It  should  be  noted  that  in 
order  to  obtain  a  rosaniline  by  this  method,  there  must 
be  present  one  molecule  of  a  ^.-toluidirie  together  with 
two  molecules  of  an  aniline  or  an  o.-toluidine,  or  one 
molecule  of  an  aniline  and  one  molecule  of  an  o.-tolui- 
dine.  Although  rosanilines  derived  from  m.-toluidines 
are  known,  they  cannot  be  prepared  by  this  method. 

A  variety  of  substances  has  been  proposed  as  oxi- 
dising agents,  viz.  mercuric  chloride,  mercurous  and 
mercuric  nitrates,  stannic  chloride,  arsenic  acid,  and 
nitrobenzene  in  the  presence  of  ammonium  vanadate 
or  ferrous  chloride.  Of  these,  arsenic  acid  and  nitro- 
benzene are  of  by  far  the  greatest  importance,  but 
the  arsenic  acid  method  has  the  great  disadvantage 
that  it  is  very  difficult  to  free  the  product  from  traces 
of  arsenical  impurities.  For  this  reason  the  nitro- 
benzene procedure  is  the  one  almost  invariably  used  on 
the  large  scale. 

PREPARATION  OF  MAGENTA  (FUCHSIN).  "  Aniline  oil 
for  red  "  consists  of  a  mixture  of  20  parts  by  weight  of  aniline 
and  80  parts  of  commercial  toluidine,  this  latter  containing 
64  per  cent,  of  o. -toluidine  and  36  per  cent,  of  £. -toluidine. 
One  hundred  grammes  of  this  mixture,  67  grm.  of  concentrated 
hydrochloric  acid,  and  55  grm.  of  nitrobenzene  are  mixed 
together  and  heated  on  an  oil-bath  to  100°  under  a  reflux 
air  condenser.  A  solution  of  3  grm.  of  iron  powder  in  the 
minimum  amount  (two  molecules)  of  hydrochloric  acid  is 
slowly  added,  and  the  temperature  then  raised  to  180° 
and  maintained  at  this  point  until  a  sample  drawn  out  on  a 
glass  rod  solidifies  on  cooling  (four  to  eight  hours) .  The  whole 
is  then  distilled  in  stearn  until  nothing  more  passes  over,  the 
residue  poured  into  500  c.c.  of  boiling  water  and  well  stirred, 
concentrated  hydrochloric  acid  being  slowly  added  until  an 
acid  reaction  is  obtained  (about  12  Ire.  will  be  required) . 
Twenty-five  grammes  of  salt  are  then  added  and  the  whole 


MISCELLANEOUS  TYPES  293 

boiled  for  a  few  minutes.  The  aqueous  solution  is  poured  away 
and  the  residue  allowed  to  cool  and  solidify.  It  forms  a 
tjrjttle  green  mass,  which  is  weighed,  ground  up,  and  extracted 
1500  c.c.  of  boiling  water  to  which  12  c.c.  of  concentrated 
hydrochloric  acid  have  been  added.  The  nitrate  is  cooled  to 
60°,  filtered,  and  the  precipitate  discarded.  Salt,  equal  in  weight 
to  that  of  the  crude  melt  obtained  after  the  steam  distillation, 
&c.,  is  added  to  the  filtrate,  and  the  whole  set  aside  for  some  time. 
The  magenta  is  then  filtered  off  and  recrystallised  from  water 
containing  hydrochloric  acid.  It  forms  dark-coloured  crystals 
with  a  green  reflex,  which  dye  silk  and  wool  bluish  red.  It  also 
dyes  cotton  on  a  tannic  acid  and  tartar  emetic  mordant. 

The  oxidation  with  arsenic  acid  is  carried  out  in  exactly  the 
same  way,  i£-2  parts  of  syrupy  arsenic  acid  (D  =•  1-8-2-3) 
being  used  to  every  part  of  red-oil.  The  oxidation  is  carried  out 
at  i8o°-i90°  and  requires  about  eight  hours.  The  dyestuff  is 
isolated  as  described  above. 

NHa 


<z>^-<z> 

CHa  Magenta 


=  NH2C1 


(ii)  The  Phosgene  Process.  A  tertiary  aromatic  base 
is  treated  with  phosgene  in  order  to  convert  it  into  the 
corresponding  ^>2-~diamino-benzophenone.  This  is  then 
either  directly  combined  with  another  molecule  of  a 
base  under  the  influence  of  dehydrating  agents,  such  as 
zinc  chloride,  or  it  is  first  converted  into  its  dichloride 
by  means  of  phosphorus  oxychloride.  These  p2.-dia- 
mino-benzophenone  dichlorides  are  blue  in  colour,  and 
probably  have  the  structure : 

C1R2N  -  C6H4 = C— C6H4NR2 

Cl 

PREPARATION     OF    CRYSTAL     VIOLET.1      Phosgene  is 
passed  into  100  grm.  dimethylaniline  at  20°  until  an  increase 
i  D.R.P.  29,943  ;   cf.  D.R.P.  27,789. 


294     PREPARATION  OF  ORGANIC  COMPOUNDS 

in  weight  of  18-20  grm.  has  taken  place.  After  standing  for 
twenty-four  hours,  50  grm.  of  dimethylaniline  and  30  grm.  of 
powdered  anhydrous  zinc  chloride  are  added,  the  whole  heated 
to  40°-5o°,  and  then  treated,  with  continual  stirring,  with 
phosgene  until  20  grm.  of  the  gas  have  been  taken  up.  The 
reaction  is  completed  by  heating  for  six  hours  to  50°.  The 
whole  is  then  made  alkaline  with  excess  of  caustic  soda,  and 
unchanged  dimethylaniline  removed  by  distillation  in  steam 
The  residue  is  filtered,  the  precipitate  washed  with  water,  and 
then  repeatedly  extracted  with  boiling,  very  dilute  hydro- 
chloric acid  until  the  extracts  are  almost  colourless.  The 
dyestuff  is  then  precipitated  from  the  extracts  by  slowly 
adding  salt.  It  can  be  recrystallised  from  a  little  water.  It 
forms  glittering  bronze-coloured  needles. 

Me2N .  C6H5  — S  Me2N .  C8H4 .  C . 


O   H.C6H4NMe2 


HC1 


(Me2N . C6H4)3 .  C  —  Me2N - <  \NMe2 

OH 


(iii)  New  Fuchsin  Process.  Formaldehyde  is  con- 
densed with  an  aniline  to  form  anhydro-formaldehyde 
aniline.  This  on  heating  with  a  mixture  of  aniline  and 
aniline  hydrochloride  undergoes  a  molecular  rearrange- 
ment and  takes  up  a  molecule  of  aniline  to  form  a  di- 
^>.-amino-diphenyl  methane.  This  when  oxidised  in  the 
presence  of  aniline  hydrochloride  gives  the  dyestuff : 


CHap  H2!NC6H6  •—  CH2=NC6H5 
• j 

CH2(C6H4[4]NH2)2 


C6H5NH2.HC1 
C6H5NH2HC1 


+0 
C1H2N  =  C6H4  =  C— (C6H4NH2)2 


MISCELLANEOUS  TYPES  295 

The  second  stage  of  the  synthesis  takes  place  by 
heating  the  mixture  for  twelve  hours  on  the  water-bath. 
On  steam -distilling  from  alkaline  solution  the  excess  of 
aniline  is  removed,  and  ^>.2-diamino-diphenyl  methane 
remains  as  an  oil  which  solidifies  on  cooling,  and  can  be 
recrystallised  from  benzene.  It  melts  at  85°.  The  final 
stage  is  carried  out  by  oxidation  with  nitrobenzene  in 
the  presence  of  ferrous  chloride  at  170°.  The  excess  of 
aniline  is  then  removed  and  the  dyestuff  salted  out.1 

Instead  of  aniline  a  large  variety  of  primary  bases 
can  be  employed. 

The  last  two  steps  in  the  synthesis  can  be  conve- 
niently carried  out  in  one  operation. 

The  methylated  rosanilines  are  violet  dyes,  e.g. 
Crystal  Violet  (see  p.  293).  In  addition  to  methods 
consisting  in  the  condensation  of  methylated  amines, 
they  can  be  obtained  by  methylating  magenta  by  the 
usual  methods.  The  technical  preparation  of  Methyl 
Violet  B  is  of  interest.  It  is  obtained  by  oxidising 
dimethylaniline  with  copper  salts  in  the  presence  of 
common  salt  and  phenol : 2 

C6H6N(CH3)2     -2.     CH20  +  NHCH3.C6H5 

2C6H5N(CH3)2 
J         +  20 

NHCH3C6H4 .  C(C6H4N(CH3)2)2 
J  HC1 


NHCH3< 


Methyl  Violet  B 

The  phenylated  rosanilines  are  blue  dyes  and  are 
obtained  by  heating  rosaniline  bases  with  aniline,  &c., 

1  D.R.P.  61,146. 

2  B.  12,  1610  ;  13,  212,  2100  ;  14,  1952  ;  16, 2005  ;  D.R.P, 
8251,  n,8n. 


/\ 

\-N(CH3)2 

—  c 

\ 

\=N(CH3)2C1 

296      PREPARATION   OF  ORGANIC  COMPOUNDS 

just  as  diphenylamine  is  obtained  by  heating  aniline 
with  aniline  hydrochloride.  The  reaction  would  prob- 
ably be  facilitated  by  the  presence  of  small  quantities  of 
iodine  (see  p.  231),  but  no  experiments  seem  to  have 
been  made  in  this  direction.  The  reaction  is  usually 
carried  out  by  heating  rosaniline  base  with  a  large  excess 
(about  10  parts)  of  aniline  to  180°  for  three  hours  in  the 
presence  of  small  quantities  of  benzoic  acid. 

THE  ROSOLIC  ACID  DYES.  The  £3.-trioxy- 
triphenyl  methanes  are  the  leuco-compounds  of  the 
aurines  or  rosolic  acids.  They  differ  from  the  rosani- 
lines  in  that  the  carbinols  are,  as  a  rule,  incapable  of 
existence,  and  pass  at  the  moment  of  their  formation 
into  the  dyestuffs. 

(HOC6H4)2 .  CHC6H4OH     -*        (HO .  C6H4)2C— C6H4OH 

OH 

1 

(HOC6H4)2.C  =  C6H40 
Aurine 

They  are  usually  prepared  by  the  action  of  concen- 
trated sulphuric  acid  on  a  mixture  of  the  phenol  and 
oxalic  acid  at  I2O°-I3O°.  The  reaction  requires  about 
six  hours  : 

,0              2C6H5OH 
(C02H)2    —    C(     +  CO    * 


C(C6H4OH)2 

II 
O 


C6H5OH 


C(C6H4OH)3 

I 
OH 

[H20 


(HOC6H4)2C  = 


They  can  also  be  prepared  by  the  action  of  formalde- 
hyde on  phenol  by  a  synthesis  analogous  to  the  new 
fuchsin  process  (p.  294)  : 


MISCELLANEOUS  TYPES 
CH2(C6H4OH)2 


297 
C6H5OH  +0 


H.iC6H4.OH 


C(C6H4OH)2 
C6H4  =  0 

THE  PHTHALEINS  AND  PYRONINES.  These  are 
hydroxy-derivatives  of  triphenyl  methane-o.-carboxylic 
acid,  the  pyronines  differing  from  the  phthaleins  by 
containing  an  oxygen  bridge  : 


HO 


,OH      HOr 


—OH 


'\ 


O 


\/ 

Pheno  Iphthalein 


Fluorescei'n 


Both  classes  of  compounds  are  obtained  by  heating 
phthalic  anhydride  with  phenols  and  a  dehydrating 
agent,  the  pyronines  being  formed  from  w.-dihydric 
phenols,  such  as  resorcinol.  The  dehydrating  agents 
used  are  sulphuric  acid  or  zinc  chloride. 

PREPARATION  OF  PHENOLPHTHALEIN.  Twenty  grammes 
of  phthalic  anhydride,  40  grin,  of  phenol,  and  16  grm.  of 
concentrated  sulphuric  acid  are  heated  to  115°- 120°  for 
eight  hours.  The  deep  red  melt  is  poured  while  still  hot  into 
a  litre  of  cold  water,  and  the  whole  then  boiled  until  the  smell 
of  phenol  has  disappeared,  the  water  being  renewed  from  time 
to  time  as  it  evaporates.  The  precipitate  is  then  collected, 
washed  with  cold  water,  and  extracted  with  dilute  caustic 
soda.  The  deep  red  solution  is  acidified  with  acetic  acid  or  a 
little  hydrochloric  acid,  allowed  to  stand  for  some  time,  and 


298      PREPARATION  OF  ORGANIC  COMPOUNDS 

then  filtered.  The  precipitate  is  dried,  boiled  under  a  reflux 
condenser  for  an  hour  with  6  parts  of  absolute  alcohol  and  some 
animal  charcoal,  filtered,  and  the  charcoal  well  washed  with 
alcohol.  The  alcoholic  filtrate  is  then  poured  into  eight 
volumes  of  cold  water  and  the  whole  filtered  through  a  moist 
paper.  The  filtrate  is  freed  from  alcohol  by  evaporating  on 
the  water-bath,  when  the  phenolphthalem  separates  out  as 
a  colourless  crystalline  powder  melting  at  25O°-253°.  It 
dissolves  in  caustic  alkalies  with  a  deep  red  colour. 

PREPARATION  OF  FLUORESCEIN.  Ten  grammes  of 
phthalic  anhydride  and  15  grin,  of  resorcinol  are  heated  to 
1 80°  in  a  metal  dish  or  crucible  in  an  oil-bath.  Seven  grammes 
of  powdered  anhydrous  zinc  chloride  are  then  stirred  in,  and 
the  temperature  raised  to  210°  and  maintained  at  this  point 
until  the  melt  has  become  quite  hard  (one  to  two  hours) .  After 
cooling,  the  mass  is  chipped  out  of  the  dish,  ground  up,  and  then 
boiled  for  a  few  minutes  with  150  c.c.  of  water  and  10  c.c.  of 
concentrated  hydrochloric  acid.  The  liquid  is  filtered  hot 
and  the  residual  fluorescein  well  washed  with  water.  The 
yield  is  almost  quantitative.  It  forms  a  deep  red  powder, 
which  dissolves  in  alkalies  to  a  red  solution  with  a  green 
fluorescence. 


INDIGO 

When  phenylglycine  or  phenylglycine-o.-carboxylic 
acid  is  fused  with  a  mixture  of  caustic  potash  and 
caustic  soda  indoxyl  is  formed.  This  on  oxidation 
in  alkaline  solution  with  atmospheric  oxygen  gives 
indigo  : 


v  COaHCH2NHr 

-»  >CO        ~- 

COOH  I      J— CH/ 

1° 


/    \ 

—  NH 

\ 

CP 

,NH— 

/    \ 

\  y 

—CO 

/ 

—       V^ 

Vo- 

\    / 

\/ 

Indigo 

\/ 

MISCELLANEOUS  TYPES  299 

The  yields,  however,  are  very  poor — from  phenyl- 
glycine  about  8-10  per  cent.,  from  phenylglycine-o.- 
carboxylic  acid  about  25-30  per  cent.,  and  a  large 
number  of  methods  for  improving  them  have  been 
proposed.  Thus  it  is  stated  that  when  the  fusion  is 
carried  out  in  vacuo  yields  of  90  per  cent,  can  be 
obtained.1  The  addition  of  certain  substances,  such 
as  barium  oxide,2  lime,3  sodium  ethylate,4  metallic 
hydrides,  carbides  or  nitrides,  metallic  sodium,  soda- 
mide,5  &c.,  also  has  a  beneficial  effect  on  the  course 
of  the  reaction,  and  although  the  composition  of  the 
alkali-melt  and  the  method  of  recovering  the  alkali 
are  preserved  as  trade  secrets,  the  sodamide  method 
is  probably  the  one  used  on  the  large  scale. 

The  method  given  below  is  the  one  most  suitable 
for  carrying  out  in  the  laboratory.  The  phenyl- 
glycine-o.-carboxylic  acid  can  be  obtained  by  condens- 
ing anthranilic  acid  with  chloracetic  acid,  or  by  con- 
densing o.-chlorbenzoic  acid  with  glycocoll.  It  is  also 
readily  obtained  by  saponifying  the  nitrile  described 
on  page  190.  Which  of  these  methods  is  actually 
used  on  the  large  scale  is  not  known. 

PREPARATION  OF  INDIGO.6  Ten  parts  of  the  sodium 
or  potassium  salt  of  phenylglycine-o.-carboxylic  acid  are  dis- 
solved in  a  solution  of  10-12  parts  of  pure  caustic  potash  in 
4-6  parts  of  water.  The  solution  is  rapidly  evaporated  to 
dryness  on  the  water-bath  with  continual  stirring,  and  the 
dry  mass  finely  powdered  and  then  added  to  8-14  parts  of 
molten  paraffin  (M.P.  60°)  at  25O°-27o°  in  a  nickel  crucible. 
Steam  is  evolved  and  much  frothing  takes  place.  The  tempera- 
ture is  maintained  at  26o°-28o°,  and  the  whole  continually 
stirred  until  it  assumes  a  yellow  colour.  After  cooling,  the 
paraffin  is  removed  either  by  extraction  with  carbon  tetra- 
chloride  or  chloroform,  or  by  boiling  the  melt  with  water 
containing  a  little  sodium  bisulphite  (to  prevent  oxidation), 
and  filtering  through  a  wet  paper.  Air  is  then  blown  through 
the  clear  boiling  alkaline  solution  of  sodium  indoxyl  until 

i  B.  23,  3437.  2  D.R.P.   179,933- 

3  Ibid.,  63,331.  4  Ibid.,  138,903. 

5  Ibid.,  137.955-  *  Ch.  Z.  1911,  397. 


300      PREPARATION  OF  ORGANIC  COMPOUNDS 

nothing  more  separates  out.  The  indigo  is  then  filtered  off, 
washed  and  dried.  If  desired  it  can  be  recrystallised  from 
aniline  or  nitrobenzene.  Yield  about  90  per  cent. 


THE  INDAMINES  AND  INDOPHENOLS 

These  can  be  obtained  by  condensing  a  ^.-nitroso- 
phenol  or  a  ^.-nitroso-tertiary-amine  with  phenols  or 
with  primary  or  secondary  amines  in  which  the  para- 
position  is  unsubstituted.  They  are  more  conveniently 
obtained,  however,  by  oxidising  a  ^.-aminophenol 
or  a  ^>.-diamine  containing  at  least  one  primary  amino- 
group,  in  the  presence  of  a  primary  or  secondary  amine 
or  phenol  in  which  the  para-  position  is  unsubstituted  : 

Me2N.C6H4.NO  +  C6H5OH  -»  Me2N.C6H4.N  =  C6H4  =  O 

An  indophenol 

Me2N.C6H4.NO  +  C6H5NH2  -+  Me2N.C6H4.N  =  C6H4  =  NH 

An  indamine 

Me2N.C6H4.NH2  +  C6H5OH  -*  Me2N.C6H4.N  =  C6H4  =  O 

An  indophenol 

Me2N.C6H4.NH2  +  C6H5NH2->Me2N.C6H4.N  =  C6H4  =  NH 

An  indamine 

It  will  be  seen  that  the  indophenols  are  derivatives 
of  quinone-imide  and  the  indamines  derivatives  of  the 
quinone-di-imides.  Although  the  indophenols  and 
indamines  are  highly  coloured  and  are  capable  of 
dyeing  fabrics  from  a  hydrosulphite  vat  (like  indigo), 
they  are  of  very  little  value  as  dyestuffs  owing  to  their 
being  loose  to  light  and  acids.  They  are,  however, 
of  some  importance  as  intermediate  products,  a  number 
of  them  being  used  for  the  production  of  sulphide 
colours.  Thus  extremely  valuable  blue  dyes  have 
lately  been  obtained  by  fusing  the  indophenols  derived 
from  carbazole  with  sulphur  and  sodium  sulphide. 
These  are  peculiar  as  they  dye  from  an  alkaline  hydro- 
sulphide  vat,  and  not  from  a  solution  of  sodium  sulphide, 
as  is  the  case  with  other  sulphide  dyes. 

As  both  indophenols  and  indamines  are  decomposed 


MISCELLANEOUS  TYPES  301 

by  mineral  acids  into  a  molecule  of  ^.-diamine  or  p.- 
aminophenol  and  a  molecule  of  quinone  or  quinone- 
imide  : 

Me2N.C6H4.N=C6H4  =  O  -*  Me2N.C6H4.NH2  +O  =  C6H4  =  O 
HO.C6H4.N  =  C6H4  =  NH  ->  HO.C6H4NH2  +O  =  C6H4=NH 


their  preparation  by  the  second  method  mentioned 
above  must  be  carried  out  in  neutral  or  acetic  acid 
solution,  in  which  case  bichromate  is  usually  employed 
as  an  oxidising  agent,  or  in  alkaline  solution,  in  which 
case  sodium  hypochlorite  or  potassium  ferricyanide 
is  used. 

PREPARATION  OF   a-NAPHTHOL  BLUE.1     Ten 

grammes  of  ^.-nitroso-dimethyl  aniline  hydrochloride  are 
dissolved  in  i  litre  of  water.  The  whole  is  heated  to  45°-5O°, 
and  at  that  temperature  reduced  to  the  ^.-diamine  by  adding 
15  grm.  of  sifted  zinc  dust,  and  then  stirring  the  whole  until 
colourless.  Excess  of  zinc  dust  is  then  removed  by  filtration, 
and  a  solution  of  12  grm.  of  a-naphthol  in  about  35  c.c.  of 
10  per  cent,  caustic  soda  added  to  the  clear  nitrate.  A  solution 
of  10  grm.  of  sodium  or  potassium  bichromate  in  200  c.c.  of 
water  is  next  added,  and  technical  30  per  cent,  acetic  acid 
then  slowly  run  into  the  well-stirred  liquid  until  it  reacts 
acid  to  litmus.  The  indophenol  separates  and  is  filtered  off, 
well  washed,  and  dried.  It  forms  a  deep  blue  powder 
which  sublimes  when  carefully  heated.  The  yield  is  almost 
quantitative. 

i  D.R.P.  15,915. 


INDEX 


Figures  printed  in  heavy  type  indicate  that  full  experimental 

details  are  given  for  the  preparation  of  the  substance 

referred  to 


ACETALDEHYDE,  96,   IOQ 

Acetals,  147,  150 

Acetamide,  222 

Acetanilide,  228,  229 

Acetchloranilide,  61 

Acetic  anhydride,  168,  174,  175 

Acetoacetic  ester.      See    Ethyl- 

aceto  acetate 
Acetone,  122 

cyanhydrin,  188 
Acetonitrile,  185,  187 
Acetophenone,  127 
Acetsalicylic  acid,  127 
Acetyl  acetaldehyde,  119 

acetone,  133 

acetophenone,  133 

carbostyril,  286 

chloride,  68 

phenetidine,  214 
Acid  amides,  218,  223 

anhydrides,  174 

chlorides,  52,  57,  64,  80 
Acids.  See  Carboxylic,  &c. 
Acridone,  269 
Acrolein,  40 

Acylamino  compounds,  228 
Agitators,  5 
Alcohol  (ethyl),  18 
Alcoholates,  147,  150 
Alcohols,  82 

dehydration,  39 

oxidation,  109,  122,  155 

reduction,  41,  91 
Aldehydeammonia,  no 
Aldehydes,  108 

condensations,  97,  117,  131, 
143,  109,  122,  155,  164, 
173,  188,  207,  233,  277, 


281,  284,  286,  291,  294, 
296 

oxidation,  155 
reduction,  41,  95 
Aldol,  117 

condensation,  97,  117 
Algol  Yellow  W.G.,  229 
Alizarine,  102 

Aluminium  amalgam,  41,  93,  255 
chloride,  31,  42,  43,  49,  121, 
127,    129,    152,    162,   173, 
274 

iodide,  80 
Amides,  218,  223 

hydrolysis,  153 
Amino  azobenzene,  252 
cinnamic  acid,  284 
aldehyde,  284 
compounds,  208 

acylation,    115,    138, 

i39>  tS*'  193.  241 
group,  replacement  by  hy- 

droxyl,  89 
guanidine,  145 
naphthalene  -  azo  -  benzene, 

215 

naphthol,  216 

diazotisation,  241,  242 
sulphonic  acid,  242 
naphthoquinoneimide     sul- 
phonic acid,  141 
phenol,  213,  221 
Ammonia,  31,  36,  108,  143,  167, 

1 68 
Ammonium  sulphide,  241,  245, 

253,  255,  284 
sulphite,  222 
Amyl  nitrite,  182,  238 


303 


304 


INDEX 


Amylene  nitrosite,  195 
Anhydro -formaldehyde    aniline, 

294 

Anilides,  228 
Aniline,  28,  209 

Yellow,  252 
Anils,  115 
Anisole,  1 50 

Anthranilic  acid,  160,  224 
Anthranol,  94 
Anthraquinone,  126,  130 

sulphonic  acid,  261,  263 
Anthraquinonoid  dyes,  93 
Antimony  chloride,  49,  59,  79 
Antipyrine,  269 
Aposafranines,  278 
Arsenic  acid,  279,  292 
Arsenious  acid,  254 
Aurines,  288 
Autoclaves,  12 
Azines,  276 
Azo  benzene,  247 

compounds,  247 

reduction,  214,  245,  277 
Azoxybenzene,  254 

compounds,  254 
reduction,  247 

BAEYER'S  synthesis,  283 

Barium  oxide,  299 

Basins,  2 

Baths,  6 

Beakers,  2 

Beckmann  change,  232 

Benzaldehyde,  113,  114 

Benzalmalonic  acid,  166,  168 

Benzamide,  225 

Benzanilide,  229 

Benzeins,  288 

Benzene  sulphinic  acid,  266 

sulphochloride,  74 

sulphonic  acid,  262,  266 
Benzhydrol,  93,  288 
Benzidine,  217,  241 

diazotisation,  241 

rearrangement,  217 
Benzil,  123,  173,  276 
Benzilic  acid,  173 
Benzo  Fast  Scarlet,  234,  236 
Benzoic  acid,  153,  159,  161 

anhydride,  175 
Benzoin,  131 

condensation,  97,  131 
Benzonitrile,  153,  187 


Benzophenone  chloride,  66 

imide  chloride,  232 

oxime,  144,  232 
Benzopurpurin  46,  251 
Benzoquinone,  138,  142 

chlorimide,  140 

dichlorimide,  141 

monoxime,  144,  196 
Benzoyl  acetoacetic  ester,  135 

aminoanthraquinone,  229 

beazuic-acid,  129,  173 

chloride,  52,  65,  98 
Benzpinacone,  93 
Benzyl  acetoacetic  ester,  136 

alcohol,  83,  98 

aniline  derivatives,  115 

chloride,  52 
Benzylidene     derivatives,     115, 

233 

naphthionic  acid,  233 
Bismark  Brown,  240 
Bleaching  powder,  61 
Boric  acid,  102,  116 
Boron  bromide,  79 

iodide,  80 

Brilliant  Yellow  paper,  34 
Brom  acet-toluide,  53 

benzene,  51,  77 

benzoic  acid,  77 

naphthalene,  55,  58 

succinic  acid,  57 

toluidine,  53 
Boiling-points,  29 
Bomb-tubes,  12 
Bucherer's  synthesis,  189 
Butyric  acid,  172 

CALCIUM  iodide,  80 
Camphene,  41 
Camphor,  124 

aldehyde,  119 

quinone,  130 

semicarbazone,  145 
Carbamide,  233 
Carbon  monoxide,  121,  296 
Carbonic  ester,  162 
Carbonyl  chloride,  74,  80 
Carbostyril,  284 
Carboxybenzoyl  glycocoll,  220 

phenylamino   acetonitrile, 

190 
Carboxylic  acids,  153 

esterification,  177 
reduction,  46,  116,  122 


INDEX 


305 


Caro's  acid,  96,  193 

Caustic  potash.  See  Caustic  soda 

soda,  31,  85,  120,  134,  173, 

285,  299 

Cerium  dioxide,  113 
Chloral,  no 
Chloranil,  59,  78,  139 
Chloracetic  acid,  50,  60 

benzene,  76 

dinitrobenzene,  204 

formic  ester,  162 
Chlorine,  50 
Chlor  malonic  acid,  60 
Chloroform,  78 
Chloropicrin,  78 
Chlor  oxybenzyl  alcohol,  no 
chloride,  109 

sulphonic  acid,  73 

toluene,  77 
Chromic  acid,  109,  122,  126,  138, 

142,  155,  157,  194,  301 
Chromyl  chloride,  112 
Chrysoidine  law,  248 
Cinchoninic  acids,  281 
Cinnamic  acid,  165,  167 
dibromide,  62 
dichloride,  62 

anhydride,  174 
Claisen's  reaction,  131,  167 
Column  apparatus,  26 
Condensers,  3 
Congo  paper,  33 
Congo  Red,  277 
Conjugated  double  bonds,  62 
Copper  bromide,  79 

powder,  37,  45,  75,  106,  109, 
187,  226,  258 

sulphate,  106,  242,  295 
Cotton  Yellow  G,  234 
Coumarin,  165 

carboxylic  ester,  169 
Cresol,  91 

dimethylol,  98 
Crystal  Violet,  293,  295 
Crystallisation,  i  5 
Cuprous  bromide,  32 

chloride,  31,  45,  121,  226 
Cyanhydrins,  147,  188 
Cyanides.   See  Nitriles 

DESICCATORS,  19 
Diacetyl  oxyanthranol,  94 
Diaminonaphthol  sulphonic  acid, 
213 


Diazo  aminobenzene,  244 
compounds,  242 
benzene  chloride,  238 

imide,  246 
compounds,  237 

reduction,  44,  45,  256 
group,  replacement  by  halo- 
gen, 74 
hydrogen,  44 
mercaptan    group, 

1 06 

nitrile  group,  187 
polysulphide 
group,  107 
sulphinic  group, 

258 
thiocyanic  group, 

1 06 

imides,  245 
Dibenzyl,  47 

Dibromsulphanilic  acid,  55 
Dichloracetone,  123 
benzoic  acid,  59 
malonic  acid,  60 
nitraniline,  55 
quinone,  59 
uric  acid,  67 

Dicyanohydroquinone,  192 
Diethyl  acetal,  150 

acetoacetic  ester,  134 

amine,  168 

malonate,    154,    166,     168, 

169,  248 
tartrate,  177 

Dimethyl  aminobenzhydrol,  101 
aniline,  38,  231 
benzophenone,  128 
sulphate,  149,  180,  183,  230 
terephthalate,  179 
Dinaphthylamine,  231 
Dinitrobenzaldehyde,  115 
benzene,  203 
benzidine,  204 
carbazole,  202 
diphenyl,  37,  46 

methane,  207 
phenol,  85 
Dinitroso  benzene,  194 

resorcinol,  197 
Dioxydiphenyl,  90 
Dipentene,  39 
Diphenyl,  37,  45,  46 
amine,  23 1 
chloracetic  acid,  67 
20 


INDEX 


Diphenyl  ethane,  36 

methane,  41,  44 

dicarboxylic  acid,  173 

nitrosamine,  198 

thiourea,  235 

Diphenylene  glycollic  acid,  104 
Disdiazoamino  compounds,  245 
Distillation,  23 
Doebner  and  Miller's  synthesis, 

281 
Drying  liquids,  20 

solids,  20 

ESTERS,  176 

condensations,      119,      131, 
132,  151,  162 

hydrolysis,  82 
Etard's  reaction,  112 
Ethane,  46 
Ether  (ethyl),  18,  148 
Ethers,  148 
Ethyl  acetate,  177 

acetoacetate,  132,  168,  169, 
248,  284,  286 

acetoacetic  ester,  134,  168 

benzene,  36 

benzoate,  18,  178 

bromide,  68,  71 

chloride,  71 

cinnamate,  168 

formate,  119 

iodide,  69 

malonic  ester,  172 
Ethylene,  40,  46 

dibromide,  68,  71 

dicyanide,  186 
Eurhodines,  278 
Extraction  apparatus,  2 1 

FAST  Green  O,  197 
Fenton's  reagent,  in,  122 
Ferric  chloride,  43, 127, 142, 151, 

194 

Ferrous  chloride,  292,  295 
Filtration,  8 

media,  10,  n 
Fittig's  synthesis,  35 
Flasks,  i 
Fluorenone,  126 
Fluorescein,  297,  298 
Formaldehyde,  97, 109,  173,  207, 

294 

Formic  acid,  156 
Formyl  chloride,  121 


Fractionating  column,  26 
Freezing  mixtures,  8 
Friedel-Craft's  reaction,  42,  127, 

162 
Funnels,  Buchner,  9 

dropping,  3,  22 

Hirsch,  9 

hot  water,  9 

separating,  22 

GABRIEL'S  synthesis,  218 
Gallocyanine,  272 
Gattermann's  reaction,  75,  187, 

258,  266 

Glucosazone,  125 
Glycerine,  279 
Glycine,  219 
Glycocoll,  219 
Glycollic  acid,  84 
Glyoxal,  276,  285 
Glyoxylic  acid,  117,  277 
Griess'  reaction,  74 
Grignard's  reaction,  87,  161,243 

HALOGEN  atoms,  replacement  by 
amino  -  groups, 
218,  225 
by   nitro-groups, 

199 

compounds,  49 
Hippuric  acid,  229 
Hydrazines,  256 
Hydrazo  benzene,  255,  256 
compounds,  255 

oxidation,  248 
Hydrocarbons,  35 

oxidation,  47,  101,  112,  126, 

137.  157 

Hydroxyl  group,  replacement  by 
amino-group,  220 

INDAMINES,  300 
Indigo,  298,  299 
Indigoid  dyes,  93,  153 
Indophenols,  300 
Indoxyl,  298,  299 
Indulines,  278 
Iodine,  49,  231,  274,  296 

chloride,  60,  79 
lodoacetic  acid,  80 

benzene,  75 

dichloride,  78 

nitraniline,  61 

xylene,  58 


INDEX 


307 


lodosobenzene,  79 
lodoxy benzene,  79 
Iron,  45,  49,  208,  247,  255 
Isophthaldehyde,  112 
Jsoquinolines,  279 

KETONES,  122 

condensations,      117,      119, 
132,   143,    164,    188,   268, 
277,  281,  284,  287 
oxidation,  155 
reduction,  41,  91,  93 
KncevenagePs  synthesis,  162 
Kolbe's  synthesis,  162 

LAUT'S  Violet,  275 
Lead,  255 

oxide,  122,  142 
Lederer-Manasse    condensation, 

97,  173,  207 
Lewco-Malachite  Green,  101,  288, 

290 

Leuco-ihiomne,  275 
Lime,  299 
Limonene,  39 

hydrochloride,  64 
Litmus  paper,  33 

MAGENTA,  292 

Magnesium,  87 

Malachite  Green,  101,  288,  290 

Malonic  ester.  See  Diethyl  malo- 

nate 

Mandarin,  216,  250 
Mandelonitrile,  188 
Manganese  alum,  114 

dioxide,  114 

persulphate,  1 14 
Mannitol  dibenzoate,  179 

hexacetate,  180 
Mannose  phenylhydrazone,  in 
Manometers,  1 1 
MarkownikofFs  rule,  63 
Meldola's  Blue,  275 
Melting-points,  28 
Menthene,  38,  41 
Menthone,  123 
Mercaptans,  104 
Mercuric  chloride,  79,  292 

fulminate,  121 

nitrate,  292 

oxide,  248 

sulphate,  i  58,  261 
Methylene  Blue,  275 


Methylene  bromide,  79 
group,  oxidation,  126 

Methyl  amine,  223 

tso-amyl  ketone,  136 
anthranilic  acid,  227 
diazoaminobenzene     sul- 
phonic acid,  244 
iodide,  181 
propyl  ketone,  136 
quinoline,  282,  285 

carboxylic  acid,  286 
Violet  B,  295 

NAPHTHALENE,  18 

disulphonic  acid,  266 

sulphonic  acid,  261,  262,  263 

sulphochloride,  65 

sulphosulphinic  acid,  259 
Naphthionic  acid,  261 
Naphthocinchoninic  acid,  283 
Naphthoic  acid,  154 
Naphthol,  87 

Blue,  301 

sulphonic  acid,  89 

Yellow  S,  205 
Naphthonitrile,  1 54 
Naphthoquinone,  138,  140,  277 

sulphonic  acid,  140 
Naphthylamine,  211,  221,  281 
Naphthylene  diamine,  215 
Neville  and  Winther's  acid,  89 
New  fuchsin  process,  294 
Nickel,  41,  42 

Niementowski's  synthesis,  287 
Nigrosines,  278 
Nitraniline,  204,  212 

diazotisation,  239 

sulphonic  acid,  264 
Nitric  acid,  17,  19,  30,  m,  140, 

iSS.  157.  199 
Nitriles,  185 

hydrolysis,  152,  154 
reduction,  225 
Nitrobenzaldehyde,  115 
benzene,  203 
benzidine,  203 
benzoic  acid,  204 
compounds,  199 

reduction,     208,     247, 

254,  255,  264,  301 
cresol,  91 
dimethylaminobenzhydrol, 

TOO 

diphenylmcthanes,  207 


308 


INDEX 


Nitromethane,  220,  248 

methylaniline,  230 

naphthalene,  203 

nitrosobenzene,  194 

oxybenzyl  alcohol,  99 

phenol,  201 

phenyl  acetylene,  47 
nitromethane,  199 

phenylenediamine,  241 

quinoline,  280 
w-Nitrotoluene,  199 
Nitrosamines,  197 
Nitrosites,  195 
Nitroso  benzene,  194 
j'so-Nitroso  camphor,  198 
Nitroso  compounds,  193 
tso-Nitroso  compounds,  198 

hydrolysis,  130 

Nitroso   compounds,    reduction, 
254, 255 

dimethylaniline,  197 

phenol,  195,  196 

tertiary  amines,  196 
Nitrosyl  chloride,  195 

sulphuric  acid,  102,  239 
Nitrous  acid,  122,  140,  194,  241 

OLEAMIDE,  220 

Oleum.  See  Sulphuric  acid 

Orange  I,  216 

Orange  II.  216,  250 

Osazones,  122,  146 

Osones,  122,  146 

Ovens  (Victor  Meyer),  19 

Oxalic  acid,  156,  277,  296 

Oxamide,  222 

Oximes,  143 

Oxybenzaldehyde,  116,  120 

Oxybenzoic  acid,  160,  163 

Oxybenzyl  alcohol,  98 

Oxygen  atoms,  replacement  by 

halogen,  64 

Oxymethylene  camphor,  119 
Oxyquinoline  (carbostyril),  284 
Ozone,  114 

PALLADIUM,  42 
Palmitic  acid,  59 
Para  Red,  237,  249 
Paraconic  acid,  166 
Perkin's  reaction,  164 
Phenacetin,  214 
Phenanthraquinone,  277 
Phenazines,  277 


Phenetole,  149 
Phenol,  87 
Phenols,  82 

oxidation,  139,  142,  158 
Phenoxazine,  271 
Phenyl  anthranilic  acid,  227,  269 
benzoate,  179 
brompropionic  acid,  63 
Phenylenediamine,  210 

tetrazotisation,  240 
sulphonic  acid,  264 
Phenyl  j'so-crotonic  acid,  i65 
glyceric  acid,  97 
glycine,  298 

carboxylic    acid,     191, 

227,  298 
hydrazine,  95,  109,  122,  146, 

257 

methyl  carbinol,  88,  92 

phenyl- azo-pyrazolone, 

252 
pyrazolone,  268 

naphthocinchoninic    acid, 
282,  283 

naphthylamine,  232 

nitromethane,  199 

oxyquinoline,  287 

paraconic  acid,  166 

quinoline,  286 
Phenoquinone,  102,  103 
Phosgene,  74,  80,  293 
Phosphoric  acid,  40 
Phosphorus  bromide,  56,  65,  68 

iodide,  68 

oxychloride,  66,  293 

pentachloride,49,  56,64,232 

pentoxide,  185,  266,  290 

trichloride,  68 
Phthaleins,  288,  297 
Phthalic  acid,  158,  159 

anhydride,  129 
Phenolphthalei'n,  297 
Picrates,  145,  206 
Picric  acid,  85,  206 
Pinacones,  92 
Piperidine,  168 
Platinum,  42,  96 
Potassium  bisulphate,  39,  125 

cyanide,  117,  131 

ethyl  sulphate,  182 

ferricyanide,   47,    157,   248, 
301 

iodide,  80 

methyl  sulphate,  183 


INDEX 


309 


Potassium     permanganate,     96, 

1 55»  l $7>  248,  266 
persulphate,  47,  193 
Pumps,  1 1 
Pyrazolones,  268 
Pyrenequinone,  137 
Pyridine,  18,  51,  175,  178 
Pyrocatechol,  90 
Pyrogallein,  103 
Pyrogallolquinone,  103 
Pyronines,  288,  297 
Pyruvic  acid,  39,  125,  277,  281, 
285 

QUINALDINE,  282,  285 

carboxylic  ester,  286 
Quinhydrone,  102,  103,  142 
Quinoline,  18,  38,  168,  175,  280 
Quinolines,  280 
Quinone,  138,  142 

di-imides,  137,  300 

imides,  137,  300 

monoxime,  144,  195,  198 
Quinones,  137,  301 

addition  reactions,  102,  191, 
253.  264 

reduction,  42,  95 
Quinoxalines,  276 

REIMER'S  reaction,  120 
Resorcinquinone,  103 
Rhodamines,  288 
Rosanilines,  288,  291 
Rosolic  acids,  288 

SACCHARIC  acid,  155 
Safranines,  278 
Salicylaldehyde,  116,  120 
Salicylic  acid,  163 
Saligenic  acid,  100 
Saligenin,  98 
Salmon  Red,  236 
Sandmeyer's    reaction,    45,    75, 

187 
Schotten-Baumann  method,  178, 

228 

Semicarbazide,  144,  256 
Semidine  change,  217 
Silver  chloride,  78 

oxide,  142 

Skraup's  synthesis,  278 
Sodamide,  132,  299 
Sodium,  32,  35,  41,  42,  92,  132, 
168,  225,  299 


Sodium  acetate,  117,  180,  226 

amalgam,  42,  91,  116,  254, 
255 

bisulphite,  89,  108,  213,  259, 
264,  277 

bromide,  57,  58 

carbonate,  117 

chloride,  57,  58 

disulphide,  211 

ethoxide,  33,  119,  132,  299 

granulated,  33 

hydrosulphite,  94,  213,  215 

hypobromite,  92,  233 

hypochlorite,  233,  266,  301 

iodide,  80 

nitrite,  139,  140,  238 

powder,  33 

press,  32 

sulphide,  211 

sulphite,  117 

sulphydrate,  211 
Solvents,  i  5 
Soxhlet  apparatus,  21 
Starch-iodide  paper,  34 
Still-heads,  26 
Stirring,  5 

Strecker's  reaction,  189 
Sublimation,  27 
Succinonitrile,  186 
Succinosuccinic  ester,  132 
Sulphanilic  acid,  264 
Sulphides,  151 
Sulphinic  acids,  258 

oxidation,  266 
Sulphonic  acids,  260 

conversion    into    phe- 
nols, 85 
reduction,  104 
Sulphur,  49,  50,  152,  236,  274 

bromide,  57,  58 

chloride,  57,  58,  152 

dioxide,  95 

iodide,  57,  58 

Sulphuric  acid,  17,  30,  40,  158, 
260,  269,  270,  279,  281,  296, 
297 
Sulphuryl  chloride,  59,  60,  73 

TETRABROMDIPHENYLAMINE,  54 
Tetranitrodiphenyl,  37 

sulphide,  152 
Thiazines,  274 
Thio  amides,  234 

carbamide,  235 


3io  INDEX 

Thio  carbanilide,  235  UNSATURATED  compounds,  addi- 
cyanic  esters,  106  tion  of  halogen,  61 

diphenylamine,  274  addition     of     halogen 

glycollic  acid,  105  acid,  63 

indigo,  151  oxidation,  47,  96 

Thionine,  275  reduction,  42 

Thionyl  chloride,  71  Urea,  233 

Thiosalicylic  acid,  106,  107,  270 

semicarbazones,  145  VANADIUM  salts,  261,  292 

urea   235  Vanillin,  114 
xanthones,  270 

Tiemann's  reaction,  189 

Tin  (and  tin  salts),  45,  208,  215,      WURTZ'S  synthesis,  35 
247.  292 

Tribromphenol   53  XANTHIC  esters,  106 

Trimethylethylene  mtrosite,  195       Xanthones,  270 

Tnphenyl  benzene,  118 
methane,  43 

group,  288  ZINC,  41,  42,  45,  91,  208,  215, 
methyl  carbinol,  101  221,  225,  247,  254,  255 

chloride,  82  chloride,  40,   70,    180,   269, 

Turbines,  5  270,  281,  290,  293,  297 


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